Harmony 880
Jeffve, I have had an 880 since they were released at Best Buy (yes I paid the "shudder" retail price.)
I have looked at the other Hrmony models as well. The 880 has lots of buttons, like most universals. I too have big hands, and there is a bit of hunting around for the right button. They are backlit to some degree.
The major plus on the 880 is the updating of drivers via the PC hookup. It is very easy to set up and I had no problems with the macros/drivers not working to control TV, Stereo, Cable Box, DVD player and ceiling fan.
Either way, I think you'll enjoy Harmony's products. The 880 has taken a beating from my kids throwing it around and it's working well.
Good luck