And while the Fantastic Four are properly giants in New York City, when done "properly", they become much smaller fish in the vast ponds they explore.

To me, the most identity-defining-image of the team is the small image of the four tiny heroes running through darkness to gain, not the safety, but potential danger of Reed's experimental rocket--as if to reach out, across darkness, to touch the expanse. 

The reason I think good runs have happened infrequently is that writers all too often think they can just throw in the catchphrases and some fisticuffs, mix, and hey presto, a good FF story. But the things I mentioned above take more thought and effort.

Knowing the voices of the characters is also key - JB in particular really knew how to script for each of the main players.  Simonson's run only misses for me in that department - in many ways, it would otherwise be my favorite, as it's beautifully drawn and perhaps the MOST cosmic of all, but something gets a little lost with the inner lives of the characters. It's telling that JB's second (I think?) issue was the street-level mystery of Johnny trying to clear the hood's name, which is on paper about the least FF premise possible.  But it works beautifully, both as a stand-alone story and as a foundational brick in a longer run.

That's the other thing - it's a team book, sure, but some of the most memorable stories are the sidebars with the individual characters, where sometimes the rest of the team aren't even on panel. Knowing whose story it really is with a given issue is a major skill.