The relaunching and partial rebooting of the DC Universe, the Green Lantern movie, and all that has me thinking about archetypal superhero universes.
1: A Semi-Coherent Mass Origin
The Marvel Universe started with this, with science empowering some deliberately, some accidentally and some by birth. Until Stan got bored and the wizard and the Norse god turned up. This can provide a useful shortcut when the players are stuck for an origin, can suggest interconnections between characters, and if the effects can be duplicated it can lead to new characters with similar power sets showing up and fighting the originals.
2: A Golden Age
Running from some time in the 30s until the end of World War II, starting with pulp mystery men in fedoras and masks and ending in Hitler-punching patriotic supersoldiers who remain an inspiration and whose scientific advances have never been duplicated seventy years later. Few of these characters are still around, unless someone wants to play one. Other historical periods include the Silver Age (the Swinging Sixties, and quietly ignore that the characters from the era are about five years older now), the Western/Victorian period, and World War One (British comics only).
3: The Big Team
If the PCs aren't the Big Team, consider what the Big Team is like. Archetypal characters, world-challenging powers, and the all-important question of why they don't solve the problems the PCs have to deal with. One trick (seen in Superhero 2044, Champions: The New Millennium and Mutants And Masterminds) is to kill off the previous Big Team so the PCs have to make a new one.
4: Secret Organisations For Good Or Ill
With superheroes running around, it makes sense that governments and other bodies are going to take an interest. It may make slightly less sense for them to come up with snappy ACRONYM names and flying aircraft carriers, but don't let that stop you. Likewise, criminal organisations may resemble Dick Tracy style exaggerations of genuine groups or shadowy conspiracies that worship snakes or something.
5: Legends Are Real! Ish.
Like history and pop culture, mythology and storytelling can be brought in and used as inspiration. (The more genres you can pull in, the better for a large setting.) So feel free to have gods, demons, vampires, King Arthur... or not, if your PCs are science heroes.
6: Space Police!
Science heroes might feel more at home with space opera - alien invaders, clashing intergalactic empires, Lensmen-style groups of alien defenders who can grant power to an Earthly hero. Rhyming oaths are optional, but if you're going full ersatz you might as well.
7: Legacy Heroes
If this isn't a universe where the PCs are among the first demonstrable superhumans, then think about who went before, and what legacy and spinoff characters might be around these days.
8: Dinosaurs And Gorillas
I trust this point needs no explanation.
9: A Plucky Reporter Romantic Interest
The Plucky Reporter is a good thing to have in a setting with lots of organised crime, espionage, and heroes and villains with secret identities. The Plucky Reporter also makes a good Romantic Interest due to a tendency to run into trouble armed only with a notebook and a stubborn streak.
10: An Archvillain
He can kick the ass of the whole team. He has his own country, or a satellite base or moon colony or something. He wears a lot of black (or green and purple). He may have a wide variety of powers, or one power used as cleverly as a PC would. Some writers will show up his sympathetic side and the reasons for his wickedness, and he'll team up with the heroes to save the world because he lives on it too.
11: Some Piker Villains
A superhero setting has mooks (nameless Snake Cult soldiers, killer robots, any number of ninjas greater than one) but it also has its jobbing villains who have a neat gimmick they use to rob banks and who show up often enough that the players will get to enjoy running rings around them.
12: Another Title Or Two
If you aren't using an established universe, the PCs being the only team of heroes can feel rather isolated. So think up some archetypes and stereotypes not represented by the team (like the Big Team or the Space Police or the hero of the Legends that Are Real or the legacy of the Golden Age or a heroic Agent of ACRONYM or somesuch) and work out what they're up to elsewhere every session. If you're feeling particularly meta, you could work out blurbs for their issues in a 'Bullpen Bulletins' page. They can appear in crossover issues as well, optionally fighting the PCs over some misunderstanding before teaming up to fight Doctor Sordid.
Now you have a universe, it's time to threaten to destroy it. (This is only recommended if the PCs are of a suitable power level. Much as I'd like to see the Punisher fight off Galactus I'm willing to admit it's a rather silly idea.) A really big invasion that might connect to a prominent PC's backstory, a big play by the archvillain, a parallel universe overwriting ours... something that'll make the PCs team up with ACRONYM, the Space Police, the mythic gods, the Golden Age heroes returned from the dead, everybody and anybody. Imagine George Perez doing the cover.