I doubt it'll do anything, or at worse something that can be easily fixed by resetting a config file somewhere. It's much less weird than even switching between Gnome and KDE.

For the most part, only KWin and KScreen and maybe Plasma Shell might care but I'd expect nothing worse than a panel going to the wrong monitor.

For your input redirection, have you tried running it in gamescope or a rootful xwayland? Not sure gamescope has much special sauce since it's based on wlroots and also runs xwayland, but they may have extra hacks for input grabbing.