Machinarium(Part of the Humble Bundle #3): - I had an issue with the click hot zone being WAAAY off from there the action was supposed to be. I was playing this on a HTPC and a 52" LCD. Having Window's font size at anything other than 100% will jack it up. Reduced from 150% to 100% and it was fixed.
Note: you will not be able to fill the screen with this game unless you are running at 1999 resolutions. Fun game though.
Fallout New Vegas: I have been having serious trouble with crashing to the desktop and have tried so many "fixes". None helped. This was made worse but the sound driver getting stuck in a audio loop that wouldn't correct until the system was rebooted. Finally, I made a shortcut that disabled desktop composition and was set to run as administrator... the game has been very stable since.
The Secret of Monkey Island - (iPad version). Problem was that I wasn't able to get any sound and the physical volume rocker button wasn't acknowledging input. The game has an issue if you have the toggle switch set to Rotate-Lock toggle. You need to turn it to Audio-Lock toggle in order to have sound function properly.