Another Harmony One user and love it. As others have said, takes a bit of set up, but once you do it properly it's outstanding. Don't think it's available any more, there's no doubt a new version?
I've tried loads over the years, but my Harmony has been going 3 years without a hiccup or issue and works exactly as I expect one should.
My kit is also made up a various bits of tech, interconnected and looped through etc with a myriad of options for inputs and sound output permutations etc but with Harmony you can set up "activities", so if I want to watch TV only with the sound from the TV then I hit the "Watch TV" option and it powers only TV up. Another Activity is set to "TV with Amp" which will fire up the TV and the amp and set the amp to the TV channel.
If I want to watch a DVD with the sound through the amp I hit "Watch DVD Amped" and it switches the TV on and to the right DVD input and fires up the amp.
Once you select an activity, the hard channel and volume buttons get set to the chosen activity so it behaves like a basic remote for the current thing you are doing, and the touch screen at the top sets up any 'special' buttons for the chosen activities devices.
It the power button and it shuts off everything at once.
As said, takes a bit to set up as you want to really think about all your activity permutations, but once down it is a great piece of lit that just works.
Along with the activities button there is a devices button, if you hit that at any point the whole remote changes to a clone of the original devices remote for things like re-tuning your TV or whatever, essentially anything other than the basic functions you need to have set up in the activities page.
Hah, I've probably confused you even more now!
Good luck.