A program called "Whatsize" can list files by size. You can find this app at versiontracker.com. Your machine is capable of holding four internal hard drives. My MDD has 4 in it and I still have three externals (for backup). As a wild guess I'd think you have lots of MP3 files? Any Videos?
I do a lot of video work and- even though I have an external hard drive where I have been keeping my work- I think there are a lot of older video files and whatnot hiding somewhere. And I was also curious about any other that might larger than I expect.