It works if you manage to get around the initial setup. The Text-to-speech narrator thing crashes the game unless you figure out the right Proton version to use (i already forgot, ProtonDB might be of help). And all my joysticks have worked ootb.
Vatsim does work, i used SteamTinkerLaunch to first install the programs on the MSFS wine prefix with Onetime Run. You can use that to run the programs too before you run the game or add them to Custom Command setting to run along the game when you start it.
Proton is basically just a version of Wine but Steam has other runtime apps like Pressure Vessel that work together making the game run. Don't know if Lutris has anything else than managing and running the apps in the Wine prefix with specified Wine version. This is as deep as my knowledge goes.