If you rank the big four using these criteria:
1. AF15, X-Men (but ONLY due to the strength of the title due to the new X-Men, the concept of mutants, and the strength of Magneto and Professor X as characters, the actual original team members aren't highly relevant today), Fantastic Four, Hulk
2. AF15, Fantastic Four, Hulk, X-Men
3. (not going to rank the key covers, too subjective, people tend to pick their favorite title or character instead of objectively comparing the artwork)
4. Hulk, Fantastic Four, AF15, X-Men
5. (err...they're all Stan Lee and Kirby/Ditko)
6. AF15, Hulk, Fantastic Four, X-Men (I'm ranking the origins here--Spidey is most iconic, the gamma accident is popular, "cosmic rays" is a bit hokey as are the powers that Stan mostly ripped off from past DC and Timely characters, and being born with powers is the easiest cop-out origin possible, Stan admitted as much, which is why he went further in developing mutant relationship to society in casting Xavier as Martin Luther King and Magneto as Malcolm X, which turned out to appeal to very few comic readers).
If you mix GSX1 into that list, the X-Men are directly trailing AF15, but it's too readily available to approach the Silver keys in price. Had Marvel not lucked out with the new X-Men, then X-Men #1 would be by far the least of the Marvel keys trailing Daredevil, as the early characters and stories weren't popular, which is why the X-Men has the dubious distinction of being Stan Lee's only major title that eventually got cancelled.