srfdude,
I just got comfortable with my Harmony. I have the 768. For everyday operation, it is the only remote I need. If and when I need to go into setup on any of my components, I'll probably use the original remotes even though I have access to all the commands.
I took me about a week of going back and forth to the website and adding things slowly. As Gonk said, check out Remote Central for a detailed review of this model. The new one, the 659, appears to be more "family oriented" as they market it. I guess it depends on how much of a power user you are.
There is high WAF appeal with these remotes because they are "activity" based. But, there is no reason the Prontos and MX-500s of the world can't be setup the same way.