I have to say, getting used to Qubes and absorbing the enormous amount of material available starting from essentially zero on security in general, how Qubes works, Whonix with Qubes, getting everything installed and configured, has been both interesting and frustrating because I can only absorb so much at a time and I've only just scratched the surface.
I have nothing that needs the degree of protection Qubes affords, so this has been more or less an exercise in curiosity for me. The lights are starting to come on. The time spent is beginning to pay off. Qubes is an amazing environment filled with capabilities found no where else that I know of. It really reveals how pale and thin monolithic operating systems like Windows, OSX, and Linux really are when it comes to security.
I hope it catches fire and becomes a mainstream environment.
There are still some rough edges and unanswered questions about the proxy, but the basics are usable in both Firefox and Google Chrome Browser.
Starting testing with the Qubes 4 advanced features next. I hope to end up with a system with a separate Qube for each use case (banking, email, GitHub, online shopping, Google, social media, etc.) where each of them has access only to the keys they need for the services they use. Still not sure if a single Qube is limited to a single key or if it can be configured to have access to multiple keys so that related accounts can be grouped in the same Qube. Will know soon enough.
Here's the link to the issue https://github.com/QubesOS/qubes-issues/issues/4661
Created a "twitter" qube that has exclusive access to the Yubikey key registered with my Twitter account. That key cannot be accessed from any other qube, just as described in the u2f proxy doc. Nice!