Worth while for people with complex setups.
For anyone with a home cinema system these remotes are brilliant as they automate a lot of tasks for you without having to use multiple remotes. Mine controls Sky+, DVD, PS3 and 360 etc and changes the TV input, amplifier input, amplifier settings, HDMI switch input etc. If you just have a TV and a PVR then living with two remotes is fine.
I have a Harmony One and find the software is fairly easy to use - you tell it what you have and then it suggests some 'Activities' such as 'Watch TV' and then it automatically does a basic setup. It took me less than 30 minutes to get 9 devices setup.