The following folder grows like mad afer windows updates. I currently clean this folder manually.
C:\WINDOWS\SoftwareDistribution\Download
Now, if you could do something to trim the unneeded bits from winsxs as well then that would be great.
SoftwareDistribution isn't 100% safe to clean as it can be cleaned the wrong way as opposed the correct way with tools like Dial-a-fix (just don't use Dial-a-fix on Windows Vista).
It is however in the unofficial and unsupported CCleaner add-on winapp2.ini as "*Windows Update Logs"