It would have to be Unova for me. Reasons being:
1. It's AMERICA. You just can't beat America.
2. Unova was the first region to include an actual storyline.
3. Unova introduced Pokemon that actually move around.
4. Many of Unova's Pokemon are incredibly cool-looking and well-designed in my eyes (Excadrill, Braviary, Hydreigon, and Haxorus, to name a few...)
5. Unova was the first region to include dynamic camera angles that really made the Pokemon world come alive.
6. Unova does not have tons of water routes.
7. Unova introduced several new mechanics to the series, including less experience points for higher leveled Pokes.