In my personal experience most games either work fine out of the box or after some tweaking, I've had a 49 inch 5120x1440 monitor for almost 4 years now. At times you'll need to use Flawless Widescreen or Widescreen Fixer to get things working, or UI mods if the game supports that. But worst case you can always try a better supported widescreen ratio or 16:9 and live with some black bars, not ideal, but not the end of the world either.