For me, the biggest change in D&D happened between 2nd edition and 3rd. Honestly, 3.0 and onward don't resemble the game I started playing in 2nd edition. Sure, the game switched to the d20 system and got far more tactical with precise movement, measuring, etc., and got much more codified. But I think the change was more drastic, because I apparently wasn't playing D&D as the designers intended - and of course, I had no way of knowing until the heavily codified rules were released.
I was a more laid back DM when I started, and I created story-driven and character-based campaigns. Players were free to come up with cool solutions to problems, not necessarily reflected on their character sheets and class abilities. In the 20+ years since I started 3rd edition, I've seen the role of the DM is the ignorant muscle of the rules, the oracle of the designers by reading the augurs of published adventures and campaign settings.
I didn't use a lot of published adventures until the complexity of 3.0 made it necessary. And they didn't resemble what I ran for my group. It was practically as great of a departure as thinking sci-fi was Call of Cthulhu and being told, "no, it's Star Trek."
Trying to present a unified experience similar to what other tables were having, judging myself and my group by the standards of the growing influence of D&D messageboards - that was probably my first "Matt Mercer effect."
I think a lot of the joy (and innocence) I had with the game ended when I left the TSR era. It was a Pandora's Box moment, and I don't think it will ever come back.