Have you toggled Hidden & System files to Visible?
How to see hidden files in Windows Vista
Once you have, then look at each folder in the root of your drive and select properties - that should show you the size of the folder and all sub-folders.
Even then, there's probably going to be a couple that you won't be able to see, unless you change security settings.
For example, in XP, the System Volume Information folder seems to have zero size, but that's because normal users - even admins - don't have NTFS rights. You can easily change that, of course, in order to view the contents (System Restore Points, in this particular case).
Once you have found the disk-hog, you can decide what to do about it - or ask for further advice.
SD