One of the problems I have with many Superhero RPGs is reactionary nature of the adventures. In a typical game, there's a problem and the heroes go and solve it. That set-up has gotten a bit stale to me. So here's an idea that I've been kicking around for a while now.
The (Fill in the Blank) Revenge Squad!
Its a classic trope in comics, a band of villains who have never worked with other before team up to destroy the hero that they feel wronged them. Off the top of my head, it's happened in Spiderman and Superman comics; if I tried searching I'm sure more would turn up.
For the Players
The players create PCs who have a grudge against a major heroic NPC. Their backgrounds should feature him very prominently, maybe even responsible for a current prison sentence. At the beginning of the campaign the PCs are individually contacted by a mysterious benefactor, with a pledge to help them gain vengeance.
I'd also suggest for the PCs to take some social drawbacks, such a a gimmick that the must do involving their crimes or must gloat before finishing an enemy. It will give a nice silver age feel o the game. Secondly, players should avoid playing psychopaths. You can play a villain with out being evil. The other players will thank you for it.
For the GM
This one is going to be a bit hard, you have to let the players take charge of what they are going to do. Preparation is the key to this, you must create a detailed world, the main hero, and if you like a group of backup heroes. One of the first things you should do is who the benefactor is,, how much help he can provide can provide and at what cost. Other questions, is there a jealous villain who wasn't invited, where does the money come from or what happens when the hero is finally destroyed.
This idea can also be used in other genres, fantasy and sci-fi pop to mind. Hmmm...hunting down Drizzt sounds like it might be allot of fun.
I recomend Mutants & Masterminds: RPG - 2nd Edition to use with this. It's chock full of super goodness!