So, I need to select the target, quit SuperDuper, Restart the Mac and everything should be OK from then on?

The external drive has never disappeared from my desktop so how can the low-level id (UUID/GUID) change?

Will SuperDuper perform a scheduled backup since I am having this problem? Any resolutions? Can I use a script in the before copy of the advanced tab to 'mount' the drive? I really need to be sure this app will work before purchasing.