I received my copy of Carcosa (hardbound) on Christmas Eve Day. Delightful book, both in terms of content and physical book.
Reading through it, I'm struck that I both like the idea of it whole cloth and don't like the idea of native PCs (as a whole) at all.
I've been watching, among other things, episodes of Outcasts and Terra Nova lately. Now, I could see options for both a standard D&D crossover or a scifi one (say, with Stars Without Number):
Destruction or near destruction of a fantasy home world / continent / what have you. Clerics or magic users establish the means to gate to the ancient city of Carcosa. Once the - seemingly abandoned - city is found to be "safe", they bring people over en masse.
Scifi could have a more traditional arrival, or a stargate style similar entrance.
I like the idea of sandboxing out of Carcosa city, with PCs needing to worry about issues with home that send them out to learn about their horrible, horrible new world. Reveals of the various natives, monsters, technology.