My roguelike experience is admittedly rather slap-dash, but from what I've gleaned from some play here and there, you're not likely to run into any all-or-nothing choices. A standard trope of the genre is that you don't know what anything does until you test it. That swirling green potion could be a full heal, or it could be poison. Drinking it and finding out it's poison is usually pretty inconvenient, but it usually doesn't insta-kill you. If it is going to insta-kill you, then there is going to be some other option: a merchant who identifies things for you at a price, or you can try throwing the bottle at enemies to see what happens, or you can feed it to your dog first (sorry rover!) or whatever. But never do you get a choice of 'do this and die, or don't do it and you have no other game mechanic to ever find out what it does'. That's not fun gameplay, that's just flipping a coin and deleting your game if it comes up heads.
Given how old-school roguelikes have such staying power, it's easy to conflate their effects with modern ones.
Nethack, for example, has dozens of ways to simply execute you if you don't know
precisely what to do. A good example of that is "stoning." (
http://nethack.wikia.com/wiki/Stoning) Dealing with stoning is a guaranteed death unless you have special knowledge that the game only reluctantly gives up.
Modern roguelikes, if they want any sort of mindshare, don't do this. I'm not saying that the hilarious and nigh-on unpredictable collision of unfortunate events doesn't happen, because boy howdy, this is also a major requirement for a good roguelike. It's just that, when it does so happen that you guzzle a Potion of Horrible Things, and you meet your end shortly thereafter, you can just about always blame yourself for it, because you have been given enough information to know better, or, as you slap yourself on the forehead, you realize exactly what inventory in your possession would have let you avoid it.
edit: for the record, I would be for an Iron Rogue setting.