If Spybot-Search&Destroy finds something, such as a rootkit, and it is deemed safe to remove, then remove it.
However, I would not recommend "cleaning" your registry. Registry keys are negligible in space. You may end up doing more harm than good. Moreover, registry cleaners don't actually "speed up" anything. It can clean and clean and maybe one day it deletes a critical Windows key out of a false positive, but by then it is too late.