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Hi Dave.  I do run a HTPC with Plex.  I currently don't have Plex added as a device to my Harmony because when I've tried this in the past I was never able to get RB and Plex to play nice.  It seemed RB was blocking the remote codes from passing through to Plex so once I launched Plex, nothing would respond.  (I was using the native Harmony support in Plex.)  I then deleted Plex device from Harmony and have just been using a Keyboard/Mouse combo anytime I'm doing anything other than EyeTV (which I have programmed through RB).
So if I understand what you are suggesting, I should add back in the Plex device to my Harmony and then simply re-assign all the buttons to be whatever I want instead of working with Plex.  But if I do that, I won't be able to actually use the Harmony natively with Plex, correct?  I was going to try this again during my "start over" process.
Also if I do this, will I have enough buttons?  The one thing I can't seem to get straight in my head is if I need one unique button for each function I'm trying to perform?  Or can I reuse buttons so long as I'm in different behaviors within RB?