I have an MX-700 that has gone belly up after several years of daily use. Previously I owned a MX-500 and I have been happy overall with both of these remotes.

The pro's I have found with these devices:
Large number of hard buttons (a must, this is by far the most important feature)
Programmable including good macro support. The ability to program through a PC is a must-have.
Simplicity--like many, I have a SO using the remote, and I need to be able to program it to switch devices (TV + Receiver inputs) at the press of a button.
Good discrete code support (TV/Receiver power and inputs)

What I don't like is the limited LCD (but again, I prefer to have as many hard buttons as possible). The serial connection has also been a major PITA because I no longer have any PC's with serial ports.

This remote will be controlling:
Tivo HD
Sony KDF-50E2000 TV (though likely a newer one in the next 12-15 months)
Yamaha VX-500 Receiver
Media Center PC

I don't care if I have to program every button by hand, as long as I can do it, save the configuration on a PC for easy editing, and make it utterly transparent for someone else to use. Because of the number of components (those above + Wii + PS3), discrete codes are essential.

I am leaning towards the Harmony One; it's right at the upper limit of what I'd like to spend. I'm kind of unimpressed with the current URC offerings, but on the other hand they are kind of the Volvo's of the remote world--boxy but good.

I do NOT need RF but consider it a plus if the price difference is not large.