it usually does not matter whether you use runtime or native. One used dependencies shipped with Steam, the other one relies on what is installed on your system. Most issues you have with running Windows games on Linux are unrelated to this.
What exactly is the issue with AC2?
For games that are not approved for Steam Deck, you must configure Steam to run them through Proton anyway. In the top menu, go to Steam → Settings → Compatibility and activate “Enable Steam Play for all other titles”.
With this option set, choose “Proton Experimental” in the drop-down below. This should work in most cases, but can be customized per-game in the game’s property menu.
Edit: Recent posts on ProtonDB suggest using proton-ge. If the setup above does not work you could try this. You can install proton-ge through RANI, then enable it in the game properties instead of Proton Experimental.
One uses steams own libraries, the other one system native ones. This might result in a performance boost for example if system binaries are newer. However it possibly creates compatibility issues resulting in game crashes. Keep that in mind when using the native launcher.
I found it here in the Forum .
you also can check if you have Overlay enabled or not to try if it helps . MagDux responded well to it