While I don't know how well it works with currently active/open or system files FreeFileSync allows synchronization based on one of 4 options
Synchronization of two locations (add/edit files on one location and the same will be done on the other)
Mirror the source onto the destination so the destination is a copy of the source
Update the contents of the source that is not located in the destination, even if the destination has files the source does not
It could be set up for "real time" so at some determined number of seconds (like 10 seconds, the default) after a file is added/edited/deleted, FreeFileSync will scan the two directories and perform whatever you chose to do.
Or you can set it off manually or add it to a Task Schedule.
It is like Dropbox or SkyDrive except you can choose whatever directories you want and it can easily back up to a mounted external drive.
On the destination, the files will be exactly as they are found on the source so grabbing single files is available.