My mom bought a Harmony a few years back when my Grandmother on her side was alive, for her to use. I had the job of programming it, with my laptop. (It plugged into USB, I think, the model that we had.)
It was kind of a PITA. Had to download the programming program, connect via USB, create a Logitech "cloud" account for your Harmony, etc.
And then, even when we had it programmed, my Grandmother still couldn't quite get the hang of it.
On the whole, I think it was a waste of money, with the "intent to simplify". For us geeks, it might be viable, but for a "norm", just wanting something simpler, I don't think that the Harmony is it. Then again, maybe they've improved over the years.