IMO its 'best practice' to close all applications that may be accessing a file that you're backing up with a sync tool and don't restart them until the sync is finished.
For calibre that would include the GUI, the Editor if you use it on files in the library, the Viewer if you keep track of reading position, and any command line tasks that operate on the libraries.
If I used FFS I would not have the issue of the small control files FFS puts into library folders because my libraries (Main, Journals, Media, Prepare and Test) are all within in an outer folder - CalibreData. I've also moved calibre's configuration folder into CalibreData via see CALIBRE_CONFIG_DIRECTORY see ==>>
http://manual.calibre-ebook.com/cust...ment-variables. So the FFS control files would be in CalibreData rather than the Library folders themselves.
on the need to check deletions before committing the sync. Absolutely essential if the sync tool doesn't squirrel away a copy of them, mine does (and before images of changes) but I still examine the results of the Compare before I go ahead. I sync all my data to a USB3 external disk every day rarely takes more than 5-10 minutes.
BR