1 part Graphic Novel Action Heroes (Justice League/Society of America, a few Marvel Team-Ups, who else even makes comics these days? Dark Horse? Archie? Shit, I dunno.)
1 part Arcane Video Game Characters (I hear Nintendo wants to do another Bo Jackson sports game. Oh, and if you can work in Sonic The Hedgehog? Say hello to video game characters who are also
1 part Public Domain Characters (Stolen from Dickens and Shakespeare. What're they gonna do, lodge a complaint from the underworld?)
1 part General Urban Legends (All adventures require at least two of the following elements: werewolves, vampires, zombies, aliens, and tentacles. See also Zombies Ate My Neighbors
1 part Corrupted Humans (CEOs, politicians, law enforcement, and any other civil service you can think of fit this category nicely.)
Choose an appropriate combination of heroes and villains. Bad guys should be outnumbered at least ten to one. Good guys shouldn't be able to triumph using the same tactics as before - the new friends they make in the crossover have to bring a new strategy into the mix.
It's also important to put the least likely partners together so as to maximize interpersonal friction. Be creative! We already know Green Arrow doesn't get along with anybody. Why not see what happens when you put Huckleberry Finn under the command of a corrupt republican contruction company owner instead?
If the "unlikely teammates" thing isn't working out, have the good guys turn against
each other. Make sure you provide a likely backstory. It can't be hypnotism or the unchaining of the seven deadly sins every time, unless you're making the token female character with the biggest rack suddenly have an onset of sexual uninhibitedness. That's always a good idea.
Not everyone who reads your crossover is going to be familiar with every aspect of each character's history. Use this to your advantage. Revelation of basic knowledge is a good way to fill a few pages; everyone tells stories and explains super-powers that are familiar to the fraction of the audience who were attracted by their favourite star, but bewilderingly confusing to newcomers. If 95% of your readers don't know that Heihachi was tossed off a cliff at the end of Tekken, you can totally reference that in a bizarre flashback sequence that seems to have no place but totally delights the few people who get a rush from the nostalgia!
Make sure you have at least one person on your creative team who wants to "interpret" the characters rather than stick to what they call "canon." Nobody else will have any idea what this person is talking about, but will definitely get behind their plan to explain how the nihilists from "The Big Lebowski" were secretly behind the creation of the super-human that later kicks ex-VP Al Gore's ass as the two fight for control over the Internet.
Above all else, make sure that the conclusion of the story slaps the reader across the face with the symbolic information that the Earth (specifically the good ol' U-S-of-A) is superior to any other nation, planet, or galaxy, whether real or imagined. Take that
, Horsehead Nebula!