*Correction on my previous post - I meant to call it THE NEW GODS ala Kirby's original run, only focus more on Darkseid.
Some of these suggestions are awesome! I'd love the Doc Doom film! The Apocalypse (Marvel) would be just as awesome - especially if it's done in a trilogy and with the original X-Men attached, bonus points if this is the central plot for X4 (but who am I kidding, that's a boat that's still sinking).
I don't know much about Loki since he is being done in Thor as it is, but that's just me. More from DC's side of things, I wouldn't mind seeing a film about Amazo, or Eclipso - both are characters that have taken on the JLA full-on and their origins are so removed from any particular 'hero' that they can be valid stand-alone films. I also wouldn't mind a rise-and-fall-sort of tale for either Bane or Doomsday - though the latter is really nothing without his battle with The Man of Steel. From the Wonder books we have Circe - a character from the Odyssey that already has films based on her - a more comic friendly look at Circe, complete with the Bana Mighdall Amazons wouldn't be a terrible idea (but of course, WW first). There's also that Chronos The Time Lord guy for all the love of continuity changes (hell, it could double as a satire for all the modern-day 'reboots' present in Hollywood). Finally, while not exactly a 'villain' per se, I think Etrigan could really add something to DC's line up.
We've seen films that are centred around notable 'bad guys' - SCARFACE is considered a cinematic masterpiece and it played that Greek-Tragedy play structure so well that even mainstream moviegoers ate it up. The possibilities are all there.