You really don't need to. If you've got less than 3 GB free you should, for future expansion. When nothing else is running except Windows and AH2, it doesn't matter how full your HD is, because it's not accessing all that other stuff.
If you REALLY want to shave a few miliseconds off (and that's being generous) defrag your entire drive.
However, as long as you have enough room for the swap file and temp files you won't help anything by saving all your other stuff to a different drive.