Pokémon became a regular subject of soft reboots starting with Ash's journeys through the Hoenn Region. Ash would get new clothes, use only Pikachu and new Pokémon, and switch out his travel companions with each new region. However, there would still be traces of older regions, especially in the early parts of Ash's new League challenges. This is where his travels through the Unova region proved to be exceptional.
Pokémon the Series: Black & White was the most committed of any series to the soft reboot. The number of changes made to the anime was unlike anything that had been seen before. It's as though everything was done to make this series feel as different from previous installments of the anime as possible.
What Big Changes Were Made to Pokemon Black & White?
The biggest change to Black & White was to the kinds of Pokémon Ash met in Unova. Normally, when Ash first arrives in a new region, it's still densely populated with Pokémon from older regions. This is so he and the audience can steadily be introduced to new Pokémon one at a time. If it wasn't done like this, Ash would have to pull out his Pokédex multiple times every episode.
When Ash got to Unova, however, it was filled exclusively with its 156 original Pokémon. This was likely meant to reflect how the Pokémon Black and White games didn't let players catch any old Pokémon during the main story; they'd have to either wait until the post-game or play Black 2 and White 2. Similarly, Ash wouldn't see older Pokémon again for a long time, at least not in person.
Ash also saw a big change to his in his travel companions. He was no stranger to traveling with new friends by this point, but he always traveled with at least one of his old friends, namely Misty and Brock. This time, however, neither Misty nor Brock were present; Ash instead ventured through Unova with Cilan and Iris. Dawn also showed up, but only briefly. Unova was the first Region where Ash mainly journeyed with a completely new set of travel companions.
Even Team Rocket was much different from how they once were. They took a no-nonsense approach to their Pokémon-stealing and villainy that made them feel a little more like a threat than they normally were. They may have still been Jessie, James, and Meowth, but they might as well have been different people entirely.
What Minor Changes Were Made to Pokemon Black & White?
There were a few more things done to make Black & White feel like a new series. The animation and art style both received a big overhaul. Ash was also made to be more like a novice trainer, for better or worse. This was also the first time in a while that a female protagonist from the games wasn't adapted into the anime, much less made into Ash's travel companion. These kinds of changes aren't exclusive to Black & White, but they do add to its feeling as a series that's been far detached from the others.
As far as giving the Pokémon anime a soft reboot went, Black & White felt like it soft-rebooted the hardest. It refrained from using older assets from the rest of the anime for as long as possible to emphasize that Ash was in a whole new region. It relied on its own Pokémon and characters to tell a unique story; the few older characters who regularly showed up were much different from who they once were. Black & White, at least early on, is so far detached from the rest of the anime that it can almost be enjoyed as its own series entirely.