My experience with unchecking was that it then removed all those books from the device. Synchronization means to make equal. When the Reader for PC sees that the device is different and you Sync it will then attempt to make the two identical thus messing up the way you have your reader set up.
It's not horrible if you only have a few books but it is indeed a nasty surprise if you have hundreds, or worse, thousands of books in your collection or you simply don't want the device cluttered with books you've already read. It just doesn't work. If you desire any semblance of order or organization that differs from what's on Reader for PC, manual is the only way to go.
As soon as you start checking & unchecking stuff to sync to the reader it will mess up whatever way you've got your books organized on the reader and even remove some you wanted on the reader and put ones on that you didn't. Synchronize means to make the two the same and that's what the program does.