Is it possible to rebuild the ~/Library folder completely? Most of the time the first step to troubleshoot an OSX application problem is to login to the Guest account and see if a problem persist. The reason for this - I presume - is that the ~/Library folder of the guest account does not contain any, possibly corrupt preference files.

Over the years of using my Mac my ~/Library folder has become cluttered with preference files and folders of applications. Some of these applications are no longer installed.
Is there a way to "start over"? Some way to delete all existing preferences, and then let the applications currently present populate it again when the application is started?
Especially the Application Support and Preferences folder is full of old, irrelevant files.

I know I could do a fresh install, but then if I restore the user from Time Machine obviously the ~/Library is restored as well.
If you log into the Guest account and everything is running as you suspect, simply create a new user (make sure they are an administrator). Log into the new account and then take ownership of the previous user's Documents, Photo's, Music, etc. folders and move them into the new profile. Depending on how many files you have to move this way it is a quick and easy way to "start over." :D