The firmware on these units is absolutely vital. I just can't stress that enough. I'll say it again

Vital. I definitely would not move forward without being certain the firmware is correct. The current firmware is 1.33. I think I started on 1.20. There is also a downloadable Tascam piece of software that monitors current firmware and software updates.
There also have been a fair amount of troubleshooting threads that have indicated USB hubs are not supported and it's essential that the connectivity is a direct USB port on the computer itself. Not specific to the Model 16 but more and more I see the typical USB cable being a culprit in interface and midi keyboard connection problems. It's happened to me and I was shocked that a fairly substantial problem went away in a heartbeat with a decent new cable. I know for sure when Arturia does tech support one of the very first questions is 'have you replaced your USB cables"? When I hear someone say that a digital device is randomly dropping audio I immediately think of connectivity.
It is true that the sample rate must first be set on the Model 16 before the software. If there is a master clock involved that of course wouldn't be the case but, clocking woes are such a thing of the distant past I wouldn't think many would want to go down the rabbit hole of external clocks. Honestly I always record at 48K /24-bit so it's just a set-and-forget thing. It's never crossed my mind that this is a game killer. I dunno exactly what you mean by "a piece of software wants to work at a different sample rate". Give me an idea of what you're referring to and I'll help if I can. I never have worked in a scenario where it's important that a project, with multiple pieces of software running, need to auto-adjust sample rates.
Anyway...if I can lend a hand, let me know.