The biggest comic book events all have a habit of completely rewriting their respective universes' continuity. Although, with that said, it's hard to say what the most impactful comic book events are, as most of them have a follow-up event in a few years that is tasked with the sole purpose of rewriting the event itself. Especially in the DC part of the industry, it seems like every event after Crisis on Infinite Earths has been an attempt to rewrite Crisis on Infinite Earths in one way or another.
Marvel, for its part, doesn't like to retcon anything officially, but that doesn't mean someone in a story won't use their powers to magically alter something in a character's life. Whether that's God Emperor Doom creating a new universe, or Mephisto robbing Spider-Man of his one true love, they're not fooling anyone over at Marvel. The reality-shaking events are still happening; they're just a little trickier about it.