Technically the 'other' option but this would have been my way.
Without having ever introduced more than the original 151, Ash and friends make it to the Pokemon League (it would probably have been about 2 years since the show start by this point). Ash goes up against the Pokemon League and defeats them, thus earning his title of Pokemon Master, for however short an amount of time. He and Misty get together (just because that was one of the things I most wanted to happen when I first saw the show some 13 years ago), Brock goes off to breed Pokemon forever, Ash and Misty go off and do separate things, but still remain very close, and there's a sense of closure yet continuation.
Basically, make it like the games endings but personalised to the characters. In the game, the goal is clear and at the end of the game you achieve it, but the secondary goal of catching all the Pokemon remains open. This should have been the approach taken with the show, IMHO.
Then again, I'm a determined OG who only ever played Pokemon Blue, only ever saw the Indigo League Series, and actually wanted the character to grow up.
Also, have something nice happen to Team Rocket, for God's sake.