Generally the notion is to have one drive being your OS drive (C:\ drive) while the other hosts <insert program/data/whatever>, that way your 'OS thrashing' isn't getting in the way of the program doing stuff on the secondary hard drive.
For what it's worth, this is less of an issue nowadays as Win7/10 is far better at background stuff that 98/XP days. In addition, SSD's make most of this notion completely moot, due to IOs being so high. You can still harvest some benefit from splitting data between two drives, but it's mostly a benchmarking exercise, and a holdover from back when we fought dragons for access to DIP switches.