I run modded Skyrim (SE) via Steam on Bazzite, and it works fine. I just installed Vortex inside the same Proton prefix as Skyrim, installed all my mods via Vortex (and made sure there weren't any conflicts) and it all worked fine. I think I might've had to install .NET as well to get Vortex going, it's been a while so I don't recall, but there should be some update guide somewhere.

RE Anti-cheat, it's not ALL of them, it's only kernel-based ones. For eg, BattlEye, EAC, VAC, and nProtect Gameguard all work just fine, but of course, the game studio will need to enable that support. Arc Raiders, Marvel Rivals, Fall Guys etc all use anticheat and they work fine.

RE KDE, I haven't experienced most of those issues. I don't use Konsole (Ghostty is far better anyways). As for Discord, Equibop is a far better client compared to official.

RE GNOME, unfortunately GNOME and KDE have never really gotten along, personally I avoid GNOME/GTK apps are far as possible.