I definitely see "groundbreaking" as setting some sort of precedent that later quests were inspired by. Some that followed even took some of these ideas and improved upon them, while others may have attempted the same and fell short for whatever reason. Also, if I say it is, that doesn't necessarily mean it was the first quest to try something in particular, but it may at least be the first I have experienced something new with.
Revenge 2nd quest by PrinceMSC, while very dated by today's standards, was very groundbreaking during the 1.90 era. Prince was always an excellent screen designer, designing screens in unique ways, and introducing other features within the limitations of an older and much more limited ZC. I believe he used trap mazes, while seemingly simple, was rather novel during the early days of ZC.
Hidden Duality, another very old quest, had multi-floor dungeons and a light world and dark world. While this was certainly based off of A Link to the Past, both worlds looked incredibly similar, while still needing to be navigated very differently. Few quests that tried the dual worlds reached close to this level of success.
The Wrath and Longing of Nemel, while having mediocre screen design, was the first quest I played with quite an extensive developing storyline, and a level structure that went beyond just the traditional numbered levels in order. There was a lot of required elements on the side. It was also one of the first quests I played with a vastly large overworld and cave system that carried over more than one map.
The Hero of Dreams was the first quest I played that had custom bosses at the end of every dungeon. It was also the first I can remember that had many humorous elements to it while still being a very serious effort in the making.
Lost Isle made usage of a lot of 2.50 features well before the stable release came out, and pulled it all off without any scripting.
I'm sure many newer quests would be groundbreaking too, but I'll leave that for others to share, as I'm sure you'll hear plenty on that. There are plenty of scripted quests out there that use scripting in a way to make the quest feel like its own engine in some way.