For most programs, it doesn't matter what drive. I installed HL2 on my non-XP drive, due to lack of space, and it worked fine. I would often install a few programs on the 'wrong' drive, forgetting to select D:/ instead of C:/.
There's bound to be the occasional program that is picky about what drive it's put on, but for all those programs that are on the other drive, you'll have plenty of space for it.