I upgraded from a Harmony One which I'd been running for a few years. The only real problem I had was migration to a new management software they had but that was as much remembering my login details as anything. Once I got in the config came over from the old remote in no time, and I was up and running within about 15 minutes.
I've had no problems with interference between the IR blasters, and the ability to change config and sync without having to plug the remote back into the USB is really helpful. Not having to rely on IR from the remote is awesome too, no more missing a device because there's something in the way, and being able to control volume when I'm sitting out on the deck!
There are a few things that I think could improve the system, such as logic for certain activities to not automatically turn off the previous one, and a config backup to make it easier to test/tweak different things without having to manually recover the known working state, but overall I'm really happy with the unit.