More power usage, need at least 64G of ram to even remotely use it as it's intended, no hardware acc by default, buggy templates, sleep is broken, uses X11 for display, dom0 is not updated as frequently as it should be and I hardly see any effort in documenting the fact that individual VMs's security matter too. That is not to say I hate Qubes. I think everyone, especially people dealing with sensitive data, should use it
Sure, assess the threat model. I would also take security over convenience anytime, just like you proposed. But for normal users, it's not that simple. I use qubes in my testbox, I love it but it's still quite niche and sadly, far from hitting mainstream