I've also been experiencing the Alt-F4 problem on a Win 7 machine using a Harmony 650. It started last night when the directional arrow buttons started repeating like crazy, and all my settings ended up getting corrupted so I had to remap everything from scratch. I'm using firmware 3.0, which isn't supposed to have the repeated key problem, correct?
At any rate, enabling/disabling the "Sequence Modifiers" option in the software didn't work for me to fix the Alt-F4 problem. What did work for me (for the most part) was enabling the "Noise Canceler" option. My guess is that there's been some kind of interference that's been causing these repeated key issues. The weird part is that it only started happening last night... I've had flirc set up and working without issue for a few weeks now, and nothing's been changed where new interference would've been introduced.