Retro City Rampage for NES did something similar (32KB program ROM, 256KB graphics ROM), but the author also developed a High Level Assembler so you he could write structured code more directly:
https://www.youtube.com/watch?v=Hvx4xXhZMrU
It's also all eight bit, obviously, so you're also dealing with nice, human manageable numbers of 0 to 255.