With a VM you are looking at a file stored on the drive you can copy to another location but would need to copy back to the same if the original becomes pooched in any way and hopefully will be recognised as valid. I've made backups of VMs that simply wouldn't load up later on a few occasions.
For your main drive and OS a full system image backup
is the smart move prior to seeing any large changes made while those temp folders are clutter! Read the guide there.
If you are finding them empty or with one or two log files dump them! It won't hurt anything. CCleaner isn't generally siomething you would run on a VM however since you rarely won't find any large clutter except for some rare occasion.
As far as the registry however it depends on the type of restoration and by what means you are referring to. If you trash the registry on a VM and it won't run then you would need to create a new one to replace it unlike a regular host OS install where you could boot live from the Windows dvd to run the system restore feature or restore a full system image while booting live.