Reliability of connection to the drives, especially during unscheduled power cycles. USB is known for random drops, or not picking the drive up before all your other services have started, and can cause the need for extra troubleshooting. Can run fine… or it could not. This is in reference to storage drives, not OS drives.
If you use WireGuard for local access, I don’t think you need to open any port on your firewall, unless you are sharing your plex with other people that do not have access via WireGuard. But I know just enough to get me in trouble, so I’m sure I’ll be corrected on this.