I have the same problem. I use a single 46" monitor set to 1920 x 1080 resolution. The game does not recognize my resolution when I tell it to use my desktop resolution, nor will it stay set to 1920 x 1080 if I configure it manually. I end up with the game visually using the upper left corner of my screen, but the mouse responds as if it knows that I have a 1920 x 1080 resolution. (Completely unplayable since you have to click where you think things are instead of where you see them.)
My current solution is to go make the manual resolution change to the prefs.ini file, then set that file to read only. It means I can't make any other configuration changes from inside the game and have them stick, but at least I don't have to fix it every single time.
I would love to see this problem solved so I could avoid having to manually tweak prefs.ini.