Several expansions on different drives <- no help, only the latest expansion exe/files is loaded, and even tho some localized and world data is loaded from the other expansions, it's really minimal.
Game and documents folder on different drives <- THAT would help. The cache files, the store items, screenshots, videos, saves and the like all go into the documents folder (normally on C, under my documents, for windows). If that and the game/expansions are separated, you *could* see an improvement.
Best solution would be to just have 12~30 gigs of ram and installing the whole thing on a ramdisk. Annoying if and whenever you have to power off the machine (requires either full copying of the whole game + expansions or reinstalling), but optimal performance otherwise.