My brother has a Framework 13 and mainly uses a combination of NixOS and Windows. Most of the time he uses NixOS, but sometimes the software he needs is broken on Nix. When that happens, he reverts to a previous version of Nix or he boots onto Windows. He has Windows installed in one of the external-drive socket thingies that he keeps plugged in at all times in case he needs Windows.

Apart from the occasional broken Nix package, he has had issues with the hyper-sensitive two-finger scrolling in Gnome (which I would say is not directly a Framework or Nix problem). Also, a while back, when I bought the computer with him, we bought Oloy RAM because it was fast and cheap, but that lead to weird crashes. Framework support helped us test the sticks and eventually we sold those sticks and got the Framework-tested Crucial sticks, which solved the problem. Finally, I remember he had to be careful about not just closing the laptop but actually clicking "sleep" and then closing it, because otherwise it would get super hot and lose a lot of battery.

Despite these struggles, he recently told my Mac-loving girlfriend that he will not get a "disposable" computer. I take this to mean he will keep using his Framework laptop.