I'm currently playing in a Freedom City campaign. The premise (which will make more sense if you read the setting) is that Omega attacked again in 2006. He, and his dimensional destruction army, were beaten back and the portals between realities closed again, but many of the world's heroes and villains, including most of the Freedom League, were killed or dragged into the Terminus (the end of all universes). The campaign started a year later, with the PCs as most of the current Freedom League (Johnny Rocket and Lady Liberty are the only previous members still around).
We now save the day in classic, four color fashion. Whether there are plots by a nemesis to learn secret identities, coalitions of super villains seeking wealth/power, bikini cheerleaders trapped on a magical island filled with zombie dinosaurs, inter-planetary political marriages being disrupted, or simple liquor store robberies, we do what we can to save the day. During an investigation of an illegal super-powered fighting arena, two of our members were killed and a third nearly so, but we managed to survive.
Currently, we're trying to expand membership of the League, create a new European League, and recover the lost soul of King Arthur.
In the future we'll probably get attacked by the machinations of the Crime League, which should be an exciting and interesting adventure against a coalition of powerful foes.
Super campaigns are harder to run because there are fewer crutches for a GM to lean upon. There are no limits to what the characters can do, the world has to grow and evolve with the team, you have to challenge the party while still maintaining the desired tone and level of realism.
My advice is to talk with your prospective players and get a feel for what kind of supers game you, and they, would like to see. Four color? Golden Age? Silver Age? Gritty Iron Age fare? A mix of all of them? Then, don't be afraid of inspirations, even silly ones. One of the more interesting, and frustrating, adventures we had was inspired by the title
Cheerleader Bikini Beach Party on Dead Dino Island; silly name, excellent inspiration for a really fun and interesting adventure.
I hope that helps some.