Rooster (for example X and Captain Marvel are not in MvC3, X-men characters will most likely not appear in MvCI) and mechanics are generally the biggest differences between fighting games

MvC games generally have a rooster based on what's popular at the time, so for example early entries of the franchise had mostly X-men characters, while MvC3 had some X-men characters (and was a little controversial since Cyclops was not in the game for the first time in the series) while adding more MCU characters (some even predicted that Guardians of the Galaxy and Dr Strange were getting MCU movies because Rocket Racoon, Dr Strange were added in Ultimate MvC3)

Mechanically the franchise hasn't changed as much as other fighting franchises since the rooster is usually what sells these games but there have been some changes to it, the big thing differentiating MvC3 to MvCI is the change from 3v3 to 2v2, the removal of X-factor (a comeback mechanic) and the integration of the Infinity Gems (most likely this game's comeback mechanic, the gems were also a mechanic in Marvel Super Heroes, a very old entry in the franchise)