Well, defrag is not going to clean up anything, so it's a waste of time.
You are talking like this appens all the time. When the hard disk fills up, what do you do to fix it? Delete some stuff? Reboot?
Use a graphical filesystem program like SequoiaView to get an overview where your disk space goes.
This constant eating of disk space could be some program with a serious memory leak - your swapfile grows without bounds. Some detailed logging going on - you havent played around with Windows system counters, have you? Normal software that you don't remember or don't know how to use - some P2P programs will preallocate all disk space for a download. A corrupt filesystem. Malware - someone is using your computer to host child porn.