Now that Warner has acquired the folks who made Batman: Arkham Asylum and are presumably going to make more games based on the DC characters, you know what story would make for a killer video game?
Superman: Emperor Joker
It'd work for a lot of the same reasons that Arkham Asylum worked: potential for dark, surreal environs, the opportunity for Mark Hamill, a hero who is continually outnumbered and outclassed, etc. But starting the game off in the normal world, fighting villains and thugs and establishing Superman's powers and world and the basic game mechanics, then stripping him of all but a fraction of his power, turning him into the villain, placing him in a surreal world under a madman's control, and pitting him against much stronger villains like Bizarro No. 1, Ignition, and Lois Lane, all so he can slowly regain his powers and take control away from the Joker, would make for a pretty epic gaming experience.
Otherwise, just a game where you're up against Mr. Mxyzptlk would be cool. But Emperor Joker would be a blast.