I'm thinking a Dungeonworld below ground and the main goal of most civilizations is to find the surface once more, having fled it in some ancient time due to the Dawn War, Far Realm incursion or some other catastrophe. The problem is its miles and miles above, crisscrossed by the Underdark, Torog's road, NEW dungeon crawl classics, and constructs designed to protect/ward the shallows. Very dungeon and exploration heavy, touching on some old school sensibilities.
Or, in keeping with the Book of Vile Darkness, an evil campaign setting where you play the monsters (return of Savage Species?) and bad guys, and the setting's monster folio could be heroic types and angels to fight. Oh, I wouldn't mind an Overlord class, something designed to command evil minions, or a sadomasochistic Torturer/Beguiler/Soulcrusher class designed to break wills.
But, maybe a little more likely, something specific in Eberron akin to what was done with Neverwinter/FR. Letting slip they'd be releasing all the Eberron books as part of a rented bundle speaks to a need for the vast collection. I bet it'll be Epic versus Neverwinter's Heroic focus, Dragon Below, Lords of Dust, that fun stuff.