So who would be good? If the Marvel or DC people wanted to create another Arkham-type franchise, what existing characters would be useful? Who's powerful enough to be fun but mortal enough that the player has challenges to overcome? Who's famous enough to sell games but not yet overexposed? Here are my suggestions:
The Grand Theft Auto games have you playing as a lawless but still ambiguously "good" protagonist against endless waves of goons, gangsters, and thugs. The gameplay actually fits Frank Castle better than it fits guys Niko Bellic or Carl Johnson. He's even got a sidekick of sorts, who would perfectly fill the "Oracle role" of the Arkham games by delivering exposition and tasks via cheap-to-produce audio messages.
This should have happened years ago. Probably the only reason it hasn't is that GTA-style games are notoriously expensive to produce.
(All of this also applies to Judge Dredd. He's ideally suited to sandbox city gameplay... assuming you've got the budget for that.)
She's got the name recognition, and yet she's not overexposed. In fact, the lady can't seem to catch a break and hasn't really gotten any meaningful screen time since the 70's. Canon-wise, her power level is all over the place, from being "as strong as Superman" to being more in line with typical street-level superheroes. I think there's enough wiggle room that you could put her up against mortals without offending the fans.
He's strong but mortal, and his shield could make for some fun gimmicks. The only strike against Cap is that he doesn't have a lot of mobility. He doesn't swing, fly, or super-jump across cities. It would still be do-able, but the game would probably need to be scaled down to a single locale, as they did for Batman in Arkham Asylum. Maybe give him mobility via parkour platforming, giving us an Arkham / Prince of Persia mashup. That could be a lot of fun.
All of this applies the same to Wolverine as well: Good power set, but the lack of mobility would be a drag in a really big open world.
Playing Flash with his actual power set would be either trivially easy (because you're always in bullet-time) or impossible (because the player doesn't actually have superhuman reflexes required to be the Flash) so we'd need slow him down from "light speed" to "just really fast compared to everyone else".
Are we ready for a game built around bullet-time? And are fans willing to see his power scaled down a bit? If so, then get this man a game.
He's been in four blockbuster movies in five years, but nobody's sick of the guy yet. Marvel should get this guy a proper game before that changes. He can fly around a city, and he's got dozens of tech-based powers that could fit into some sort of unlockable upgrade path for the player. He's usually depicted as being bulletproof, but I think players would be willing to accept firearms (but not fists) as a credible threat. He's got Jarvis for exposition and his weapons-making company is perfect for attracting (or even creating) villains for him to fight.
The only downside is that whoever ends up voicing him is going to end up standing in the shadow of Robert Downey Jr., and that's a long shadow. They could just just hire Downey, (assuming he's interested) but then they're going to run into the expectation that this is "Marvel Movie Universe" Iron Man, which brings a bunch of complicated baggage. Movie Iron Man is awesome because of his chemistry with his supporting characters, and that might not work so well in an action game.
His "mooks" would probably need to be robots or paramilitary guys in space marine armor, but those fit really well into the typical Iron Man story.
Like Moviebob said a year ago, Enough with the Batman Already. We've got tons of great superheroes out there. People don't love the Arkham games because they have Batman in them. People loved Arkham because the combat was satisfying, the writing was solid, the gameplay was varied, and the visuals were gorgeous. Rather than flooding the market with more Batman, let's get some of these other heroes out there and give them the same treatment.