Some of the more common messes I see:
* Attempts to 'optimize' the registry resulting in corrupted files
* removal of 'temp files' that were still in use
* old update files that were removed, but a later rollback needed them (Particularly with beta versions of the .net framework as needed for some beta versions of games)
* sometimes the load order of drivers will change causing systems with 3rd party disk encryption software to fail to load properly
Most of the messes just cause applications to fail to load properly (Or put them into a loop of 'This application isn't installed, install now?' 'This application is already installed, installation failed' because it can't find specific registry keys but finds its files.
IMHO, even the most remote risk isn't worth the possibility of increasing boot times by a few seconds or freeing up a even a few gigabytes of disk space.