I have not used an MX500, but I do have an opinion. The "activity" based approach used by the Harmony is much superior to "macro" based approaches for anyone (read wife and kids here) who does not know the details of your system. More buttons would be nice, but the loss here is minor compared to the gains with the Harmony. Specifically, the implementation of "Help" button function on the Harmony is great for resynchronizing the remote and the system. You simply provide a yes or no answer a set of simple questions. In other remotes you need to figure out which component is out of sync, know the specific setting that needs to be changed, and know how to use the remote to change just that setting.

Bottom line, my wife can now use our home theater system without asking me a lot of questions and without getting angry at me all the time for making her life so difficult.

Ed