We're all aware of this. One thing I've found that often seems to be the cause is if you have Caps Lock on. Normally hot keys don't care, but obviously Settlers hot keys are case aware, so just a tip for anyone to try next time their hot keys don't work. It's not a complete fix - sometimes they still don't work, but mostly I've found it's the caps lock causing Letter hot keys not to work.

As for number hot keys - sometimes the ones in the main part of the keyboard will work when the numeric pad ones won't. Other times, neither will.