Considering I've got 5 60 GB hard drives that are almost full, finding stuff can be a pain. I've got the folders grouped by catagory (Applications, Games, Movies,Pictures, etc) and then within each folder I have sub-folder further refining the catagory (CD-R Tools, Action Movies, Shark Pictures, etc).
I only have 3 visible windows partitons (3 drives are on a RAID). On of them is my boot, which ONLY has Windows and programs on it. Data goes on the other drives. I format/reinstall frequently (I'm in the middle of it, actually) and having everything on seperate partitions helps.