I've been thinking lately of a couple of interesting ones:
-One is inspired by New Wave Science Fiction -- the characters find themselves in a biological landscape, everything around them is some kind of tissue or organ, only impossibly large and baroque. There's a huge 3D space of twisty little passages with a constant wind blowing in and out to represent the lungs, for example; somewhere else, there's an endless forest of trees crackling with lightning, representing the brain. The rivers are full of giant blood cells and deadly antibodies. Anyone who falls into the heart is liable to be washed away and find themselves in desolate landscapes without any human presence at all. I'd run this in a heartbeat, but I can't figure out where to take it from there -- whose body is it, and what are the PC's doing there?
--Another is inspired by the cool Dungeon World setting, Inverse World, where everybody lives on floating rocks above a golden sun, and the rain comes up from below, then drips back again. Inverse World is a setting where things just work like that, but I really like the idea of playing in a setting where the apocalypse was gravity suddenly reversing -- most of the people and animals were outside, behaving normally when gravity failed and they took the long fall. Some lucky people were inside or on the underside of rocks or in airships or could fly, and so some small fraction of the population survived to colonize what were formerly the barren undersides of the worlds, eternally in darkness since the sun is now below them. (This is actually part of the Inverted World setting -- farmers grow crops that hang down from the underside of floating rocks, since that's the only part of the land that has both sunlight and rain. Being a farmer is dangerous work.)
Some of the planetoids and floating islands themselves broke up under the strain, shattering into dust and dangerous flying meteors. Hell, maybe most of civilization once lived on some great floating continents, most of which have now shattered. But if you've got ship, you could cruise along the underside of a dead land, cautiously climbing out into upside-down towers and buildings that still somehow cling to bedrock, looking for treasure and daring the wrath of the insane, cannabilistic apes who have colonized the inverted ruins....
I'd probably have the PCs come from either a dying little rock in the fringes, or an ancient airship left over from the Great Breakdown, constantly in need of repairs, constantly moving through the wreckage like a steampunk version of Battlestar Galactica.
By the way, I have a severe phobia of falling, so this is the scariest possible Apocalypse for me... your mileage may vary.