There is no definitive answer to this question, as the anime’s storyline and characters are constantly evolving. However, some key events that may have an impact on one’s understanding of one Piece may include: the Battle of Marineford, Luffy’s capture by the Marines and his escape;
Chopper’s creation; the Whitebeard War; and Gecko Moria. So, while there is no one episode that definitively changes everything, there are several episodes throughout the years that can significantly alter one’s understanding of the story.