Of the three, much as I like Moon knight, that book has baffled me the most. So it seems like the purest spec play of the three.
Punisher has always seemed to me to be a two-dimensional (albeit cool) supporting character, but he grew a fan base and carried series. He may not be at his all-time peak, but it's a first appearance of a significant character.
I like IM55 as a key, but it's so much more than Thanos (and Drax, for that matter). Yes, the big guy is the lynchpin, but it's the launch pad of all Starlin's cosmic Marvel contributions of the bronze era, and that's pretty far-reaching. I think it's a key, but to view it as a key solely because of Thanos' first app diminishes its importance.
I see the FF52 arguments but think it gets more of a pass than say FF45 because it's Marvel's first major black character. Look at Dell's Lobo or GL87; this is enough to buoy it. I still say Josie 45 (first black character in an Archie comic) is underappreciated, given the status of the other three keys in this "first" genre.
Fun stuff to kick around. Of all of it, Bats 121 baffles me the most. Sure, tough in grade but many books are. It's status just seems outsized compared to Mr Zero/Mr Freeze's status in the Batman rogues gallery. He's barely an afterthought for a long time. But obviously I'm missing something that the broader collecting market sees.