I'll list a few quick ones. In B/W 2:
- You start in a new location, and the storyline is different. There are several new locations.
- Lenora, Chili, Cress, Cilan and Brycen are replaced by Cheren, Roxie and Marlon.
- Iris is the new Champion, replacing Alder, who can be fought post game.
- Black City and White Forest now work a lot differently. The Black Tower and White Treehollow are there.
- Take place 2 years after B/W. The storyline makes several references to the player who defeated Team Plasma in the original games.
- Team Plasma are now a completely different team now with a new goal. N is no longer of their side; in fact (spoiler warning), he saves your life at one point in the story.
- The Regional Pokedex has almost doubled in size.
- The Cold Storage is replaced with the PWT, and Route 10 is no longer accessible. There is a new Pokemon League and Victory Road.