If you run CCleaner regularly you don't need to open disk cleanup at all. Does CClean run through at present OK?
Without making a silly point, there must be many files open just running Windows, but have you had a look via msconfig to see just what is running at startup?
Sometimes when things get difficult it can make a difference to come off the net, then disable AV and firewall while you try disk management procedures such as disk cleanup or more particularly the Defragmenter.
How much free space is actually available on C: has there been any major change recently to hard or software?