I'm currently running a RAID 0 setup with two drives in my rig (I did this well before I multiboxed). I have 1 folder for the main and 1 folder for all the clones. The data folder for the clones is linked to the main's data folder via a symbolic link (do a search on the forums here for NTFS junction points), so it's really the same data. Having the majority of the data (aside from the UI addons) in the same place means you get a lot of cache hits when loading all 5 at the same time, so it only has to access the disk once for a lot of the data. My load times for 5 are barely more than for one.

A separate physical drive for each clone would be fastest, but who has that much room in their case.