HOX/POX is over and its 12 issues is an instant classic and a pantheon-level X-Men story. That made me realize that Hickman is set up to do what no writer in Marvel history has done. Not since Stan Lee and even Lee is arguable. He is going to be the first writer in Marvel history to defining runs on all three of Marvel's biggest teams : Fantastic Four / The Avengers / X-Men .

I mentally went over a list of other writers who might come close and other examples. I request the help of fellow CBR posters to help me/correct me/qualify me on this.

So looking at major writers who have done defining works on multiple teams and characters:

Lee-Kirby
1) Fantastic Four -- Natch.
2) The Avengers -- The early issues until Kirby left and then Lee handed over to Roy Thomas. Important for sure, and key moments like Loki instigating the Avengers' formation, and Cap being found in a block of ice and becoming the leader were done then. So it's too short for a run but it's defining.
3) The X-Men -- Lee-Kirby's X-Men is revised now and again for nostalgia reasons and it introduced many key elements and so on. Some can argue that it's defining while others will disagree. I don't think it's defining but I'll leave that to others to judge.

After that, though, it's debatable if we've had writers do defining runs on one or both titles, leave alone all three.

-- Roy Thomas worked with Dave Cockrum on X-Men and on the Avengers with other artists. Of the two, I think his Avengers run is more defining and long-lasting. But Claremont has said his run on X-Men was underrated. Thomas wanted to work on Fantastic Four but I don't think he ever got a long run on the title and even if he did, it was part of the long slump in the title between Lee-Kirby and John Byrne, which brings me to...
-- John Byrne was an artist on the X-Men, and a defining artist at that. He was also a close collaborator and plotter with Claremont. It's well known that Byrne resented and disliked the direction Claremont was taking the X-Men and as he said in a recent interview, "I didn't like what Chris was doing, but it was popular and for most readers that was becoming the X-Men. So if I didn't like what Chris was doing, it meant I didn't like the X-Men". Byrne then went on to do the second major run on Fantastic Four as both writer/artist. So it's ambiguous with him if he qualifies on two titles since he served different roles in both. Byrne later worked on the Avengers later but I don't know if his run there was great. Chris Claremont later worked on the Fantastic Four in the '90s and that wasn't considered especially memorable.
-- Roger Stern is interesting. He served as line-editor of X-Men during the Claremont/Byrne run. He then became writer of a defining run on the Avengers (arguably the greatest), and followed that with a brief stint on Fantastic Four which was most notable for the issues in which Stern brought Jean Grey back to life from the cocoon in Jamaica Bay. So it's all tangled there with him. But I think Stern got 1 out of 3.
-- Mark Millar for better and worse wrote a defining Avengers story (CIVIL WAR) and he had a run on Fantastic Four which I think had some good issues. I don't think he wrote a major X-Men story however.
-- Brian Michael Bendis wrote a defining Avengers run (New Avengers), and he wrote a story (HOUSE OF M) that was significant in X-Men publ. history even if it wasn't especially good or influential. But he didn't do much with Fantastic Four.

So that leaves Hickman, who has done a defining run on Fantastic Four (from Dark Reign:Fantastic Four onwards), a defining run on the Avengers, which ended with a landmark crossover (Secret Wars 2015) that was a finale for both of those runs. Now he's doing X-Men, and starting with HOX/POX which is one of the greatest X-Men stories ever. So Hickman wins.