Okay, with a HUGE patch for the game about to release, fixing tons and TONS of stuff and totally redoing the overall balance and difficulty progression, I thought this might be a good time to write up a bit of a guide for this, to help players learn about it. I'm going to be explaining some things that the game does not explain, as well as pointing out some notable items, weapons, and enemies to watch out for.
This is going to be long, so feel free to just skim a bit. But I'll try to keep it concise.
I'm NOT going to go into the extreme basics. You should know what health pickups do and how to buy things from shops and all of that. This isn't a manual. That being said, lets get to it:
Mechanics and Objects
Missiles: Learning to use these is perhaps one of the most important things in the game. The game certainly tells you how to fire them and all... but learning how to use them WELL is a whole other matter. There are two major things you should be doing with missiles. First, searching for Health Shards. These appear in bombable blocks (only destroyable by missiles) that have something blinking on them; in some cases these are easy to spot, in others they are hard to spot. Destroying one will always drop a health shard. You can see how many health shards you have up in the upper left of the screen. Collect enough, and you'll gain 1 additional max HP. Keep doing this as much as you can, as this will add up over the course of the game.
But thing number two to use missiles for is DEFENSE. When a missile impacts an enemy bullet, it explodes, destroying that bullet and others in the immediate vicinity. This means that if you're about to get hit, a quick missile launch could save you some damage... or be the difference between victory and defeat. While collecting health shards and opening up bombable walls to get items behind them is important, NOT DYING is way more important... so try to keep missiles on hand for this. Particularly when you get into the late-game and enemies start getting... unpleasant.
The "slow" button: There is a button/key that you can hold down to chop your movement speed in half. USE THIS. Many patterns in the game... particularly on Hard mode... are designed to be... pretty thick, and the best way to deal with patterns like that is to keep your movements careful and controlled. The faster you move, the more likely you are to smack into things. Against many foes, you will *need* to do this, or you're likely to die. Learn to use this in all situations; it's one of the most important things you can learn in the game.
Secret Rooms and Sacrifice Rooms: These rooms contain powerful items for you.... but are hidden. Unlike in, say, Isaac, there is no easy way to really tell WHERE they are unless you have specific items or perks. Instead, the main way to find them is to destroy special bombables.... the ones that contain the health shards. If you destroy one in a room that's connected to a secret, that secret door will suddenly open and the game will make a funky sound. THis is all the more reason to go after health shards! Sacrifice Rooms have you pay max HP to get powerful items, and the cost of these goes up each time you buy one. Secret rooms, on the other hand, contain FREE items, however you can only choose one item from the room if it contains more than one. The game's absolute most powerful, OP, broken gizmos are typically reserved for secret rooms only, yet all sorts of neat stuff can be found there.
Generators: One thing I wish the tutorial explained is generators. A generator is a big machine with red pulsating tubes on the sides; it sits there and doesn't move, and only appears in rooms that have active hazards such as lasers, turrets, and other things. It takes three missile blasts to destroy a generator, and when you do so, all of the traps in the room will instantly shut down. This can be a real lifesaver in some rooms... so consider doing this, as that missile cost could turn out to be very worth it. But there's one other thing generators do: if a room is cleared of enemies and there's a generator around, the traps in the room will NOT shut off like they do in normal rooms. If you want them to ever shut off in that room... you must destroy the thing.
Phasing blocks: These are blocks that sorta phase out as you shoot them; they never totally vanish but instead become this sort of foggy mess, that you can completely pass through, however, unlike shootable walls, these will return to solid form after a time. There is a trick you can do with these that might save you from some of the game's most aggressive enemies; anything that actively pursues you will actually consider phased blocks to be solid, and will just refuse to pass through them, either going around, or simply stopping. This means you can halt things like Bulldogs or even the deadly Charger in it's tracks, and take them out at your leisure.
Glass breakables: These, obviously, are the blocks that break in one hit, dropping an item of some sort when you do so. But a special property of these is that unlike shootable blocks, enemy bullets will not break these. So until YOU break them, you can use them as cover. This can be important in some rooms depending on what you're up against.
Consumables: One of the biggest tips I can give to anyone is to USE YOUR CONSUMABLES. In the versions prior to now, consumables weren't very good. Not really worth getting and using. That, however, has changed. Now, they are powerful items that can help a ton if used right, and as with any powerful item, they can be the difference between victory, and being in 10000 pieces. I'll explain the uses of some of the best ones:
Healing Nanites: I forget the exact name, but this consumable fires out a bunch of heatseeking shots that hunt down enemies, and upon impacting them, instantly transfer some HP to you. This is the game's most powerful healing item, and can take you from 1 HP to max through just one use. You REALLY want these.
Tactical Nuke: This thing fires straight ahead, in whatever direction you're aiming, and does TREMENDOUS damage to anything caught in it's blast, except you. Designed for use against bosses, it's also useful for dealing with super dangerous "heavy" foes such as the dreaded Sideshot. Seriously, this thing hits like a freight train.
EMP missile: Again I forget the exact name, so sue me. This is like the nuke, with a massive blast, except instead of doing monstrous damage, this will just heavily screw with enemies that are caught in it's blast. They'll be slow, with much worsened fire rates, and generally unable to do their job of making your existence difficult. If it's dangerous, it can be made less so by firing one of these in it's general direction. This is particularly useful against the powerful swarmer enemies that appear in the late game.
Guide to the Galaxy: Shows you the layout of the entire floor, aside from secrets. Use this whenever you can get one to help you decide what path you want to take through the level, and where you want to go first.
One Way Barrier: This drops a huge wall right in front of you that stops enemy bullets. More importantly, it will sit there and continue to do this for quite some time, and it's really very wide. This is an EXTREMELY strong defensive item, for dealing with bosses or heavy enemies or huge hordes or... anything really. You, of course, can fire right through it.
Time Machine: Possibly the game's most powerful item, this rare consumable regenerates the current floor, completely restarting it (and restructuring it) as if you'd just gotten there. The benefits here are obvious; redoing a floor means a chance to grab EVEN MORE items and things, and get even more EXP, on your run as a whole to take with you into the end game. This item used to be fairly common like any other consumable and was OP as heck; in this build, I placed it into the Secret Room only to seal up it's brokenness. But it's just another reason to try to seek out that room. If you manage to get this little gem, the best way to use it is to COMPLETELY clear out the floor you're on, including defeating the boss, before you use the item (don't actually leave the floor!). That way you maximize your gain.
Experience Machine: In every shop there's a machine with a green glow to it; it looks kinda like part of the background but it's a device you can interact with. Standing on it gives you the option to pay a small amount of credits to get some experience points. When you're stuffed with money for whatever reason.... this is a great place to spend it. The amount of EXP that the thing gives scales up over the course of the game, so that you can always get some benefit out of it. And the reason to do this is simple: The faster you level up, the earlier you get access to powerful perks that can make or break your run, and perks are powerful things that you definitely want. When using these machines though, it's best to spend a similar amount of credits as you would when buying a useful item. When I use one of these I typically dump about 70-80 credits into it.
Modules: One of the most important choices you can make in the game is which module to carry with you. Modules are typically pretty darn powerful, but the tradeoff is that you can hold only one at a time. Often stronger than most normal items or perks, these can do all sorts of loopy things to help you. But selecting the right one to go along with your build is important. Don't just grab these as you see them... consider what you already have at the time and decide carefully.
Notable Items and things
Guardian Blade: Possibly the SECOND most OP item in the game, this is another one that I sealed away, locked into the Secret Room to prevent it from crushing the rest of the game's balance. If you spot this item... grab it. This blade slashes in front of you in a short arc every couple of seconds.... destroying all bullets it comes into contact with. The ultimate defensive item, this is a game winner for sure.
Railgun module: This is a great module for any build, really, adding a sort of triple shot to your weapon and increasing your overall power. A very solid item, you cant go wrong with this.
FTL module: This is similar to the Railgun in that it ends up being a very "overall" power increase, but this is even better. Very highly recommended... consider taking this one with you if you spot it!
Fire radiating module thingy: Bah, like I can be expected to actually remember the names of everything. This module radiates fire around you, a constant small burst every couple of seconds or so. The short range of this thing might make it seem kinda weak, and originally it was. But it got a power boost, you see. Now, it's GREAT at dealing with pursuing enemies that get too close, or.... well, anything that ends up too close to you for any reason at all. This can hit pretty hard and can destroy most smaller foes in one hit.
Map of the Stars: A sacrifice shop item, this one maps out every single floor for you, showing you the locations of every single room. But what's really important here is that it ALSO shows you the locations of not just sacrifice rooms, but also secret rooms.... you know, the room with the free stuff that could be crazy powerful. Having a full map of every floor is a pretty strong effect in this game as it is, but having knowledge of THAT right away is even better.
Glassbreaker: Also in the sacrifice shop, you get a 50% base damage boost from this thing (which is pretty darn nice), and then also the ability to instantly destroy shootable blocks simply by touching them. This actually can be a great help in battle, allowing you to dash right THROUGH those barriers instead of having to slowly drill your way through them with your gun. NOT getting stuck on those can often be the difference between dodging an attack, and getting 20 bullets up your nose.
Big Leaky Battery: One of my favorite items, this gives you a HUGE increase in max energy.... but will cause it to slowly drain at a constant rate. This item can allow you to fire your energy weapons much, much more often.... which is a very good thing... but it very much favors aggressive play. When you've got this, go nuts with that energy weapon of yours right away at the start of each room, so you flatten things that much faster and get as much benefit from the thing as you can. This item should NOT be used if you are carrying the Guardian Blaster, which the Flame Tank mech starts with. But for most energy weapons? This is pretty darn good.
Antimatter: An item with a similar theme, this reduces all energy costs by 20%, and can allow you to fire heavy energy weapons a lot more often. For weapons with a very low cost per shot though... not so good.
Riot Supressor: An energy weapon that fires a single shot that moves forward a bit, stops in place, and then fires 10 squillion bullets in all directions that have the ability to pierce enemies. This thing has a high energy cost, but it's very powerful and GREAT for dealing with hordes.
Destiny: This item can appear either as a boss drop, or in secret rooms. You REALLY want this. This is an increase, and a nice big one, to ALL of your stats. Easily one of the best items you can get, and with zero downsides.
Phantom Bullet: This energy weapon fires a triple shot that can pierce walls. .....do I really need to explain why this is good?
Decimating Power: This thing costs a TON of energy to use.... don't bother grabbing it if you don't have at least 100 max energy. That being said, this may be the strongest of all of the energy weapons. What it does: Instantly strikes every enemy in the room, taking them down to half of their current health. THAT is pretty freaking strong. However.... this has no effect at all on bosses, so keep that in mind. That being said, this is a VERY effective attack.
Blaze Cannon: Ah, the Blaze Cannon. Everyone loves to hate it. A sniper, this thing fires a single blazing shot that travels THROUGH walls, and puts out a trail of flame behind it that makes it pretty tough to dodge. If you spot this thing's signature attack.... and it's hard to miss.... this should be a priority. Hit it with everything you have ASAP. Note that if you strike the projectile with a missile, you get rid of the entire thing. On Hard mode, this enemy gets some.... interesting additions to it's arsenal. More ways to annoy you!
Bulldog/Bullrush: One of the most aggressive baddies in the game, this thing has no range attack, but instead just CHARGES at you as soon as it has you in it's sights. It is very fast, and what's worse, it'll sorta lock you down once it has you in it's jaws! Be prepared for attacks by these at the start of any room; they're perhaps THE enemy that's most likely to get the jump on you. Run away while firing at them to take them down.
CrossClaw: A very common enemy, this stationary annoyance fires a sort of slow green zig-zag beam. The problem: This beam completely blocks your shots and can travel the entire length of a room, and this enemy fires fairly often. It's not particularly deadly, but it really has the amazing ability to get in the way at the worst times. Note that you can actually fit BETWEEN the beams if you need to. Don't waste missiles on this guy though; just get to the side or behind him to take him out, but deal with particularly aggressive foes BEFORE attacking him.
Bubble: This enemy only appears on the final 2 floors, and is a unique sort of threat. Bubbles will sit perfectly still until you get into their sight, at which point they'll start following you around, throwing out a constant barrage of bullets. But that's not what makes them deadly: when you destroy a bubble, it releases this massive shockwave of bullets. Nearly undodgable, the only real way to deal with this attack is to pay attention to how much HP the Bubble has left, and when it's about to pop.... dive away and get behind cover until the shockwave passes. But it's not over yet! When a Bubble pops, it leaves behind an enemy called a Larva, which roams around slowly firing shots in all directions. It has high HP and can quickly fill an area with pain.
Swarm: Not really a specific enemy, but more of a TYPE of enemy, a swarm is a group of enemies that orbit a single "core"; all of these, including the core, tend to look identical. The core is what does the actual moving, the others simply orbit it. Swarm type enemies tend to put out a high volume of bullets due to their numbers. The important thing to know about all swarms: If you destroy the core, all of the orbiting things will be destroyed as well! Good luck with that though, it's usually pretty difficult to get at the core without drilling through a bunch of it's friends first. There is an exception to the "destroy the core" rule. A particular boss called Metal Legion uses swarm-behavior orbitals during it's first phase, however.... you cannot just pop the core to take them out. Instead, the boss is invulnerable so long as any of it's orbitals are still there. You have to defeat all of them in order to progress to the second phase of the battle.
Pearl: This is a "jumpscare" enemy; it wont move or attack until you get close enough and is invincible until it activates. Pearls fire a huge solid wall of shots at you, over and over. Their attacks are very predictable, but they're excellent at filling small spaces with them. They are particularly dangerous in corridors. It's best not to engage a Pearl (or any jumpscare enemy, really) until other foes are gone.
Krill Splitter: Another jumpscare, this one covers the ground in bullets that move all over the place at random like a bunch of deranged ants. Try to keep moving when dealing with one of these; you don't want the "source" bullet (which creates all of the others) to hit you. Try to keep some distance between it and you once it's active. Since it creates so many shots, it's worth using your energy weapons on.
Persistence: These fire extremely nasty homing shots. Large GROUPS of homing shots. Which bounce off of walls. The best way to deal with these is to constantly circle them until it's defeated.... and then hide out while waiting for it's bullets to dissipate.
Sideshot: One of the nastier enemies in the game, this thing fires shots to it's sides that then fire even more shots at you in a funky constant spread pattern. This enemy is the bane of many players, new and experienced. However: It WILL NOT FIRE if it doesn't have line of sight. Use this to your advantage. Like many enemies it fires even more shots at you on Hard mode.
Flak Cannon: This mobile monstrosity is one of the most dangerous things you can encounter in the game. It fires a thick pattern of shots, sort of a slow, staggered spread, and then into that it fires a SECOND pattern of entirely different shots that do something else. Never attack this while other enemies are around. ALWAYS clear the area before dealing with this monstrosity. There's no easy way to deal with this guy... one way or another, you'll have to learn to dodge the chaos it puts out. On Hard mode, it fires more than DOUBLE the number of shots it does on Normal mode. I refuse to apologize for this. Fortunately for you, this does not appear until the final couple of floors in the game. Try to save your energy weapon for this guy, and dump the entire thing into him when you attack. You want him gone ASAP once you do engage him.
Red Hunter: This is a miniboss, and I want to mention him because of his special ability: As you attack him, he gets FASTER. Attack him enough, and he'll be much faster than you.... and he'll be on top of you in a moment. The trick to this fight is not to hit him too many times in a row. Get some hits in, then stop firing, make sure he's back to normal speed, and then fire again.
And that's all for now!
I'm not going to go into bosses, as giving hints and such for them requires a ton more explaining than any other element in the game. If there's a particular boss you're having trouble with, I'd be happy to make a brief demonstration video showing the technique to defeat it on whatever difficulty you're playing on.
And yes, I know... there's plenty of other items and enemies I could mention too. But these are based on my own experiences with the game, so I chose them based on that; other players may have different ideas about what the best items are and what the most dangerous enemies are.
And of course.... if I mentioned TOO many, this would be an even longer post!
If you have any questions about anything at all in this game.... please don't hesitate to ask.