This dual P-III CPU Dell Precision workstation has the OS on one physical drive, and everything else, including MP3, MPEG, my graphics and image library, and software downloads w/upgrades located on a separate pair of mirrored IDE RAID drives. I also have a 120gig USB external drive, partitioned into four separate drives, to do periodic backups with.
I've had too many crashes over the years, and I make it a point of reformatting and re-installing my OS and core apps once a year, anyways. I use CCleaner, EasyCleaner, and Lavasoft AdAware, but even the best registry cleaners don't get rid of all the junk that finds its way into the stack.