Let's all accept that keyboard + mouse won't happen, at least in any form recognizable from the first game, and get back on topic...
There are a handful of tweaks that could improve the beginning of the game. Broadly, they fall into 2 categories:
(1) Choose better defaults for certain controller types. Several reasonable defaults have been mentioned, based on similar titles. One or more of these should be submitted to Maven for voting.
(2) Tweaks to the "feeling" of certain inputs, to improve the usability of the first-time players. Proposed features include a "stand still while aiming" or "moonwalk" button, and improving menu navigation.
Also, there are other PC platformers that don't use the mouse. Right off the top of my head, Cave Story comes to mind.
The controls on Cave Story are awesome out-of-the-box. I can't recall having to remap any of them.
But changing the entire monster design is also a big project. The thing about most 8 direction shoots is the map and all the rooms get designed in a specific way to be tackled. Whilst the AVWW rooms are not too bad most of the time, the monsters are what kills it when they just get free reign all over the place.
IIRC, Metroid solved this with less-mobile monsters. In the early Contra games, the only thing that moved fast were weapon powerups. Not sure about the Castlevanias, but I remember the books were really slow and protoplasms only applied status effects (SOTN).