Hi, I have the same problem. The GUI doesn´t save any changes anymore. If I try to delete or reprogram any buttons, the messages from the GUI are fine, but everything stays the same. Any changes to the Advanced Settings, like Sleep Detection and the Inter-Key Delay aren't saved as well. Even after clearing the whole configuration, all keys are still mapped as before.
Running Windows 8.1 and using a Harmony 650 with FLIRC-Profile btw. Already tried running FLIRC as administrator and reinstalling FLIRC, didn't help.