Just got the Harmony 880 today, so I won't post a full review yet, but aside from the fact that the new Intel-based Mac beta version of the software doesn't actually work (thank the gods I have more than one Mac), the setup was relatively painless. I've probably got an odder assortment of devices in my setup (e.g. using a Mac mini for CDs and MP3s) than most people, but with a few back-and-forths between setting up the remote with the Mac (it connects via USB) and testing it in the living room, it seems everything is pretty close to the way I want it, aside from the VCR, which steadfastly refuses to work.
Once I get things set up, I'll give you a little more info; but aside from the VCR, so far, so good. This may very well be the holy grail of universal remotes once I finish tweaking it to my liking.