A book of themes, which would have all the existing ones (that are setting-neutral) and a bunch of new ones too, all balanced against each other. Wouldn't have to be a big product, but I'd like all that information in one physical source. Maybe include backgrounds too.
A book of traps, hazards, and terrain features. Include a bunch of skill challenges too, with an exploration vibe. And different types of environments, and the dangers PCs would encounter there. For DMs to flesh out the non-combat aspects of adventuring.
A monster book focused on the Far Realm and aberrants, much like Lords of Madness.
More classes focused on the Shadow power source. Classes with a cool theme and mechanics that we haven't seen before in D&D. A dedicated Necromancer class, as others have mentioned. I'd like to see more monsters-as-classes, like a lycanthrope. Maybe roll all this up into one product and call it the PHB 4.
Heroes of the Astral Sea, followed up with a 4e-style Spelljammer product or quasi-campaign setting.
A book focused as PCs as leaders: rules and advice for governing a city or nation; building castles, temples, and wizard towers; mass combat; followers; and that like. And lots of adventure hooks. As much a product for DMs as players.
A Steampunk sourcebook, with fantasy mecha, firearms, gadgets, and other cool stuff
DMG3, for the sake of completeness
EDIT: Oh, and an Unearthed Arcana-type book with lots of optional rules for everything.