Pokémon Gold & Silver.
Fun Fact: It was not the success of Pokémon Red & Green that cemented the franchise, but the success of Gold & Silver, which led to Pokémon's expansion into a global media powerhouse.
As a gamer, I still list Gold & Silver as the best title in the entire series, as well as my favorite. This was the title that revealed there are more than just 151 pokemon, thus igniting a whole new approach to the game. This was the title that revealed there are more than 15 types, and the title that introduced Special Defense, thus changing the way we battle forever. This was the first and still only main title that allowed you to explore more than one region. This was the first title to be a sequel.
No matter how far we go, and I think with Gen 9 we will see just that, I don't think we will ever have a Pokémon game - or video game in general - as grand as Pokémon Gold & Silver.