I'm quite late to the game here (just got my Flirc) but what I have a similar situation for which I've come up with a workaround.
I have a Vizio smart TV with a Vizio QWERTY remote, which I am using for both Flirc and the TV. When I switch to the TV's Netflix app for example, I don't want the keys I use in Netflix to register with the Flirc/XBMC. I also want to keep my PC running (so no sleep/wake solutions).
Originally I wanted to find a way to detect (for example with EventGhost) when my HDMI was switched from my HTPC to another source. That didn't work for me. The next best thing for me was to lock the system while I was using another input.
I ended up finding a little AutoHotkey script/program called LockScreen (http://www.deanhouseholder.com/projects/lockscreen/). Basically it locks the screen and keyboard input with a hotkey, and then unlocks it with another hotkey. Very easy to configure with the INI file.
Since I generally use the Input button to switch between inputs, I mapped the lock hotkey to the Input button and the unlock hotkey to another button on the remote. Now when I switch back to XBMC from a different source there is a simple black screen that says "Locked" - I just press my unlock button and I'm back in business.
For now I'm quite happy with this solution, although it would be great in the future for Flirc to have a more intuitive way to "disable itself".