Many apps will not fully install on drives other than C (or more correctly the drive that Windows is on).
And that doesn't address the problems folk have with the iTunes library on other drives. I strongly suggest the biggest drive for C.
Bob
I have a desktop (Hp Pavilion 743G - "Pentium 4") with an 80GB hard drive (with Windows XP) that includes iTunes. I have added 250GB hard drive (with a Windows XP Pro clean install). The 250Gb hard drive (C) is master and the 80GB (E) is slave. The computer boots up to the "C" drive. When click "my computer" to access the "E" drive, open "program files", and open iTunes, I get a message saying "uninstall iTunes & then reinstall iTunes and the file will not open. I goal is to delete all program files from the "E" hard drive (printer, etc,), install them on the "C" hard drive, and only have iTunes on the "E" hard drive. How can I accomplish this easily?

Chowhound
Comic Vine
GameFAQs
GameSpot
Giant Bomb
TechRepublic