Currently I'm running my main on a two-drive RAID-0 array (which is also where the system swap file is), and a pair of clones on each of two more drives. This seems to be optimal for my 4 drive setup. I had been running my swap file on the same drive as two of the clones, but noticed greater load lag on those two than the rest. After moving it to the RAID array, I saw a great improvement on those two with no noticeable difference on my main.

Edit: I wanted to also add, you should NEVER use more than one folder per drive due to caching. If you only have one drive, all 5 from one folder is the only way to go.