So much of the decision surrounding remotes and other control devices centers around who the users are and what they're doing with it. Specifically..
1. Are you designing primarily for DVR/cable STB replacement?
2. Are you the only user, or will wives/children using it?
3. Are you trying to replicate the ease of use of a typical cable STB?
4. What is your comfort level with technology? That of the other users?
I've been using HTPC's for about three years now. Both of them are used by my wife and 7 year old son. My son took to the system very well. I use Harmony remotes for "typical" uses and a DiNovo mini for keyboard/mouse functionality. My wife is ok with the Harmony, but only after many months of exposure to it. She won't touch the mini. The idea of using a keyboard & mouse in front of her TV is still foreign and very uncomfortable.
So, I designed for that situation. There is no better or worse.. just what works for you and the people you share your home with. Ultimately, if the system is hard to use, it'll sit in a corner and collect dust.. which to me would be the ultimate insult to my investment in time, money and research.