Already have it set up that way plus Alt+F4 for fast quit of Plex HTPC (assigned to a spare button on my Harmony 650 through Flirc).
I only have Plex HTPC running when in use (full screen, not windowed).
As for PFW, I can navigate with the K400+. Maybe it is just the way Windows is set up for me ?
Specifically, on Plex HTPC though, the UI just is not intended for close up use (sitting in front of a laptop/desktop).