I would absolutely -adore- new settings for D&D.
I thought Ghostwalk and Eberron were interesting back in 3.5. But they were -so- intently focused on creating as many new races, classes, prestige classes, and spells that they really didn't bother trying to make new campaign settings, much less effort incorporating all the wild new mechanics into a new setting.
We've seen Magepunk but how about, and for those of you who have never looked over at my avatar or name this -might- be a shock... Steampunk?
A Pseudo-Victoriana campaign setting focused largely on Urban Adventures in a world that isn't dramatically mapped out beyond a few specific large communities and the names of some neighboring nation-states..? Somewhere where much of the map is left largely empty for GMs to fill in as they see fit, but where those handful of cities are -deeply- involved and carefully mapped to provide players with a hellacious quantity of potential directions to go? I don't think D&D has released an Urban Campaign Setting in... ever.
How about a largely aquatic "Waterworld" style campaign setting (concept, not the movie. Love ya, Costner, but damn you had some stinkers). Aboleths swimming free in the ocean, endless archipelagos and small islands rather than big singular landmasses. Whole campaigns designed in an episodic manner as the crew of a ship "Maps" a series of islands, each one with it's own theme and style.
Take a note from Midnight and make a Points of Light campaign setting in a world where the Evil Gods have won and conquered the world. Where paranoia and questions of loyalty and intention are features. Where players can't be -sure- their neighbors won't turn them in for being decent folk.
In an absolute Script-Flipping, how about a setting where Psionics are normal and Wizardry and Sorcery are rare, and much-maligned?
How about a setting where Druids, Barbarians, and Rangers are largely Eco-Terrorists eager to destroy the "Civilized" lands and return them to the Natural World? Where player Druids are threats to Law and Order even when they're -not- murderous plant-hugging monsters and are "Betrayers" of the Natural World in the eyes of other Naturalist characters.
How about a setting where the whole thing is focused around a World-War? Where the majority of the continent is -at war- during the game, and players spend their time either being a part of or avoiding the militaries of the world, searching over battlefields for lost treasures, or building up keeps and castles to defend themselves and their loved ones from the endless trading of land by making deals with each side as they come.
More settings would be amazing.