I personally will always have a soft spot in my soul for Hoenn, so I'll have to say third generation.
The region itself was radically different from any other (being mainly tropical), and the pokemon designs reflected this. It was just really diverse.
On top of the regions design, it implemented a lot of new things, like natures, abilities, field weather, differences in pokemon (Spinda), and diving.
Overall, third gen just holds my heart. :)