Alternating drives in target NAS when backing up? Any advice?

In your scenario, each set of drives will be a "virual NAS"  All configuration information is stored on the drives, so swapping the drives out is tantamount to swapping the whole NAS.  There are a couple of exceptions:  OS updates and cloud services (ReadyCloud, ReadyDR).  If you update the OS with one set of drives, it will only update the drives currently installed.  While the other set should update when you install them, it's a risk.  I believe that some of the Netgear cloud services are tied to serial number, so that could cause problems if you use those.

All in all, a NAS is not really intended to be used that way and you are taking a risk.  But are you likely to lose both sets of drives?  Probably not.

FWIW, the fire department is going to soak your garage if your house burns down and your NAS will probably be a loss.  And burglers can be more clever than you give them credit for..  But you would have your other set of drives you could put in a replacement NAS if they are stored off site.  A cloud backup service is probably a better plan