"Impactful" is a pretty general word but I'll do what I can here:
- Some of my players still talk about the Star Wars game I ran probably ten years ago now. That's a good sign it had an impact. Sometimes having a definite start-middle-end in mind is a good thing and makes your game stronger.
- I ran a Greyhawk campaign 20 years ago with just 3 players running back and forth between Dyvers and the City of Greyhawk that comes up more often than I would have expected it too. That's a good sign. Sometimes fewer players lets you focus in on them and good things happen.
- Different parts of my 3rd and 4th edition games come up with different players. This often involves a character death, a TPK, or a character doing something really risky or stupid. It's not always the character who dies or did the thing either - sometimes they were just a witness and it was still pretty impactful.
For me there are a few candidates - TPK's, unexpected character moments that really changed a game, and wildly different approaches to adventure situations than I ever expected.
The one I would rank at the top though is from a recent M&M session that I documented here. It was a new player, a new and rather unusual character, a tense situation, and something that just developed by chance and it was awesome, easily the most interesting thing to develop in my last ten years of superhero gaming and a high point among all of my sessions regardless of genre or system.