I honestly think you are indeed overthinking things a bit.
I happen to use both Qubes and Home Assistant, and they both are awesome software products for their own use cases, but I don’t really see any need to combine them, at least the way you are considering it.
May I ask why you are thinking that with the Home Assistant Blue you would be connecting anything to the Internet? The way I got to know Home Assistant is as a home automation solution which is very well suited for security- and privacy-focused people that Qubes-users happen to be most of the time. In fact, Home Assistant heavily advertises the “no cloud required” aspect itself.
I have installed Home Assistant on my own hardware (well, actually it’s a VM on my home server but that isn’t of importance here) and thus, I do not have detailed knowledge about the Blue appliance, but from what I saw on their website, it is basically a vanilla home assistant installation bundled with hardware that is very well suited to handle most of the usual tasks.
Yes, Home Assistant does offer some optional “online features”. However, these are only meant to make interaction with your setup more comfortable and are in no way obligatory.
But you don’t seem to have doubts about Home Assistant itself, only about how and where to install it.
In that case, a dedicated physical machine, be it the Blue appliance, a Raspberry Pi or the old NUC of yours, would in my opinion be the most secure setup you could go with. First, physical separation is more secure than “just” virtual separation in a VM of its own, because there could always be a hypothetical escape-to-hypervisor exploit which breaks the barrier of VMs.
Second, using a physically separate NUC, installing Qubes on it and then using this device exclusively for running Home Assistant just doesn’t add any more security.
The security of Qubes comes from separating things on one single system. If you are running only one thing (your Home Assistant installation), there is nothing to separate it from. You will only increase the administrative overhead, because you will have to connect your smart home devices to your home assistant installation somehow, and that will inevitably mean to deal with firewall rules and punching holes in your Qubes system just to make it work at all.
My opinion is: take the “Qubes way” and apply it to your home network on a larger scale. Don’t separate VMs on one computer, but device groups in your network. Create separate subnets for your smart home devices and confine them in there, together with your Home Assistant installation. A decent firewall appliance, e.g., pfSense, will help a lot. Work with VLANs, create firewall rules and make sure that communication flows exactly the way you want it. This is how to achieve the best security for your home network. After all, Home Assistant (or any other home automation solution) is just a single piece of a “smart home”.