I feel like there’s a lot of potential for exploration in the worlds of 80s/90s side-scrolling beat-em-ups. There’s an almost post-apocalyptic setting implied in many of them, where social disorder has led to a societal collapse. You see this in Double Dragon, for example, when you leave the urban environments and there’s a sort of unrecognisable lawless wasteland. Not that the cities seem to benefit from the rule of law!
You don’t get to see much of those worlds in the games themselves with their sharp focus on walking right and beating up punks, but I think there’s some fun to be had there.
I suppose there’s some crossover with cyberpunk, but the beat-em-ups tend to be less futuristic and less obsessed with technology, sort of like a 1989 that never was.
I don’t know how it would work mechanically. The obvious route is something like Feng Shui with elaborate martial arts mechanics, but part of me thinks it’s worth exploring a more abstract approach to combat. Then again, fistfighting is probably the central transaction of the genre, so you would probably want to emphasise that in play.