To give an alternate perspective.
I'd been after a Harmony remote for absolutely years and finally made the plunge but after setting up all devices and configuring the easiest Harmony layout possible, it simply couldn't beat the speed/convenience of dedicated buttons on a regular remote.
I didn't mind using it but getting the family to use it was impossible. I even setup multi-action buttons which worked very rarely since it only takes one device to miss a command and a four button tasks turns into a twenty (i.e. simple one 'Watch Cable" will power on TV, switch to correct input, power on cable box, or a complicated one 'Watch a BluRay' would turn on the plasma, fire up the bluray, change the video input on the plasma, then press eject).
In the end since we use only the TV + FireTV remote 95% of the time, we just keep those out and keep the Harmony stored away.