Need more info
It depends on how you want to clean it
Clean it bare bones and completely wipe it no
It also depends if you have more than one partition (C: drive D: drive etc)
You can clear off a NON-System partition no problem as long as no software is installed to that drive.
The only other way to completely clear off a system drive
without reinstalling would be to GHOST an image of your drive... but that wouldnt' accomplish much as you'd just be right back where you started
What are you trying to accomplish?
Are you getting slowdowns? Need more storage space?