I split my drive into 3 partitions.
<--A--><-----------------------B----------------------------><----C---->
A = C: 10gb [Windows] (NTFS)
B = D: ??gb [Games/Progs/Etc] (NTFS)
C = T: 5gb [%TEMP%/SwapFile] (FAT32)
C: gets fragmented the most, with it having windows on there and all, but with it only being 10gb it takes only a few minutes to defrag.
T: is FAT32 as that has less overhead (you can change the drive letters in administrator tools) and holds my temp folder (change the temp folder settings in control panel) and the swapfile (edit swapfile settings so min and max are the same value so windows doesnt mess with it once created).
D: Is just the rest of the drive, meaning when I install a program I manually edit the directory it goes to, ie D:\Games, D:\Progs.
Just a suggestion anyway