Go for it. I had great experience with it so far with my Cachy VM in Proxmox.
The only true headaches I faced were related to usb passthrough and bluetooth headphones when accessing it “directly”.

Remotely though, using Sunshine/Moonlight, it was a breeze.

Does protondb list games which specifically block running inside VM as well?

Isnt that the usual initial userbase? Your average person probably doesn’t go around trying new platforms.