For backups on my Mac, I use CCC. For backups on my PC, I use a Acronis true image and also Genie backup manager pro. All of these back up programs have an incremental feature which will only backup changes that have been made. I assume that the NAS has its own backup software since we are not talking about a specific type of operating system such as OS X or windows. Putting both of my external drives in a two bay case sounds like a great idea. Because each external drive is only 2TB, I would need to back up certain data on each drive as there will not be in enough room in the future and I hope there's a way to do this.Check the specs of the NAS, many have 2 USB ports. I don't know the exact model you're looking at, but the Synology 213, 214 and 215 all have 2 USB ports on the back. I think (never done it) that you can direct certain data to be backed up in specific locations.
Could also get a 2 bay USB caddy and use this for the backup? Should be pretty cheap.
USB 2, USB 3, doesn't really matter. The initial back-up would be a complete data transfer. I believe I'm correct in that subsequent backups function like time machine in that they only copy changes, not the whole archive