Don't think that works for super-villains. Over-saturation devalues their appearance and the characters themselves. Look at The Joker in the Arkham games.
It wouldn't be over saturation because characters like Rhino, Doc Ock, Electro, Shocker, etc, would be random occurrences. Regular minions would level up and become more powerful, but they'd never quite reach the threat of a Green Goblin or Punisher. Certain districts would be more prone to crime sprees, but having to constantly stop Shocker or The Wrecking Crew, or The Enforcers while free roaming through the city wouldn't devalue their appearances, especially if appearances can stack. Ie; you're swinging around the city, and your Spider-Sense lets you know that trouble is nearby. You swing to the threat, and it's the Rhino, causing shenanigans. Normally, this type of event would be a boss fight, but because the location is randomly chosen, you're forced to improvise a way to stop Rhino.
But just as you're getting the hang of it, The Vulture appears out of nowhere. Again, a random trigger, spurred by the fact that earlier in the game you stopped him, and now he holds a grudge. So you're now wrestling with two threats, and it compounds when the local gang mooks get wind of your ground and air battle, and send in reinforcements for Vulture and Rhino. That could easily be an emergent gameplay scenario that would be spurred by something like the nemesis system.
Devaluing a super villain would be if he showed up in every Spider-Man game after this one, and is always the focal point. Like Magneto in the X-Men movies, and The Joker in every Batman game.
There are villains in the Spideran universe that will always keep coming back and posing a threat. The Enforcers, Shocker, Mysterio, Kraven, Electro, Hammerhead, etc, etc, are all kind of low level threats that Spider-Man is always dealing with. You'd want to save the big dogs like Wilson Fisk and Green Goblin and Venom, Hongoblin, and Carnage could be single game main antagonists, while this other guys can be mini-bosses or side quest villains, or random encounters from the nemesis system.
EDIT: regarding the nemesis system in a superhero game, it would obviously be tweaked and not an exact copy/paste of the Mordor one. It's not like players don't die while playing these types of games, but it would be more along the lines of defeating enemies or a particular gang enough times raises the hostility level of the gang. After reaching maximum irritation, perhaps they send out a super tough hired gun to take out Spider-Man, maybe they even hire a named villain like Electro to kill you. Defeating their top level lieutenant wilL lower your heat with that gang until you raise it again, and the cycle begins anew. The top guy you defeated will hold yet grudge and become your nemesis, and maintaining constant heat with the gang he's affiliated with will see him becoming outfitted with more and more gear and weapons to make him/her even more deadly to you.
Something along those lines. Again a 1:1 copy of the nemesis system wouldn't work in a game like this, but the core idea of building up rivalries with minions would.
