The best fighting games like Comix Zone are Streets of Rage 4, Shank 2 and Guardian Heroes. Below are 5, each with the reason it is here — and, at the end, what filtering to fighting costs you.
Filtering to fighting means you want a contest with a clear answer — you got it right or you did not. It is the right filter when what you liked was reading an opponent.
What you get: A skill ceiling you can actually see yourself climbing, and the shortest feedback loop in games.
What made Comix Zone worth playing in the first place is covered on the full list. This page is the fighting part of that answer, and only the fighting part.
The best modern beat-em-up, with hand-drawn art of its own.
Comic-book 2D brawling with the same visual attitude.
Saturn brawler with branching paths and huge personality.
A 2D action game built entirely around a visual conceit.
Ink-drawn 2D action with an aggressive style.
A first few hours that can be discouraging alone. Fighting games are far better with someone at your level than against the internet.
Specifically, these are strong answers for Comix Zone that are not fighting games, so they are not on this page:
The full list is on games like Comix Zone — 9 picks, no genre filter.
Streets of Rage 4. The best modern beat-em-up, with hand-drawn art of its own.
No. Comix Zone released on the Sega Genesis, but a recommendation is only useful if you can play it, so the picks above span platforms and eras. What they share is the genre and the reason.
Much less than they were. Modern control schemes, rollback netcode and real single-player modes have changed the on-ramp completely in the last few years.
One opponent against one, or one against many. They share ancestry and almost nothing else — the picks below say which each one is.
By hand. Each pick was written for the full Comix Zone list first, on what the game actually does, and this page is the part of that list that is fighting — never a genre tag lookup, which is how "best racing games like Super Mario 64" used to be a page on this site.
Or read the fighting guide for where to start in the genre generally.