Personally I organized in the following manner:
C:\ OS and essnetial apps - Single fast drive
D:\ Secondary Applications and Games - Partition of a second drive
E:\ User profile storage (including documents, desktop, favorites, etc) - currently part of the second drive
F:\ Music Media storage and drivers - External drive connected via FireWire800
G:\ Backup offboard drive for profile and essential system snapshots - External drive connected via USB
M:\ Optical Drive one - DVD-RW & BluRay burner
N:\ Optical Drive two - DVD/RW & BluRay reader
O:\ Video media share - Network file-share from a server
P:\ Picture storage - Source/Photographer, Genre, Collection, Subject, and revision organized - Also network share
Z:\ superfetch drive - speedy flash drive for system superfetch requests.
Most of these drives also have different applications sorted by type (Office, Internet, Utility, Media, etc) or the media sorted by genre (Full Movies, TV eps, Genre, Series, etc). I can get really picky about it and have spent days reorganizing things on occasion.
Honestly I do so much manual management that I'll be looking forward to making numerous specialized Libraries in Windows 7 and simplifying my storage structure quite a bit. For those of you also using Windows 7, how are you liking Libraries and other new features for organization. I have it on a few machines around the house and only recently have started getting into how to organize the media I have on the network shares via the library functions. I've been going through the whitepapers on it and some of the stuff is pretty well done. The universal search in Vista (when you index things) is pretty good, but does take a bit of memory and resources. The indexing is a bit leaner in 7 from what I've seen.
