You didn't think I'd let 12/12/12 pass without doing this, did you? Time to celebrate the twelve most notable twelfth issues in comic book history!
In no particular order (well, the first ten are in no particular order)...
The conclusion to Alan Moore and Dave Gibbons' epic story, as we see the ramifications of Ozymandias' seemingly crazed plan. How do our heroes handle the fallout from their former friend's actions? Can they keep quiet for the betterment of the world? One of them definitely can't, so how do they deal with it? Fascinating questions answered in this dramatic and compelling finale.
Fantastic Four #12
The first crossover of Marvel superheroes. Pretty damn notable, right?
Crisis on Infinite Earths #12
The (as it turned out, temporary) tend of the Multiverse as 50 years of continuity was wiped out to create a fresh new world for Barbara Gordon to be crippled and Black Canary to be tortured!
Alpha Flight #12
The death of the Guardian! One of the most shocking comic book deaths of all-time! It is not so shocking now because of how often major characters are killed nowadays, but at the time, John Byrne killing the ostensible lead of the comic book was a real shock.
Amazing Spider-Man #12
The first time Spider-Man was unmasked! Great Lee/Ditko tale of Spider-Man trying his best to fight a more powerful foe (something that comes up a lot in Spidey stories, and this was one of the earliest uses of the trope).
Squadron Supreme #12
The finale to Mark Gruenwald's epic visualization of what it would be like if superheroes tried to handle things "realistically." Things would unsurprisingly go poorly.
Captain America Annual #12
The first appearance of the Battling Bantam!
Okay, I guess this actually doesn't belong on this list. Never mind. Carrying on!
Marvel Super-Heroes #12
The first appearance of Col. Yon-Rogg and Medic Una!
The first appearance of the Juggernaut!
Red Rackham's Treasure
The twelfth Tintin album, it introduced Professor Cuthbert Calculus and is likely the best-selling album of the entire Tintin series! Wow!
The reveal of the Fourth Man!
The classic Jesse Custer/Jody fight to the death.
Basically the real beginning of this long-running series. Young Mark Grayson thought that his father was the Superman of his world, but in reality, his father was part of an alien invasion. His father wants him to join him and he is not above beating an alliance out of his son. Can Mark stand up to his father and perhaps temporarily save the Earth? A brutal but moving issue by Robert Kirkman and Ryan Ottley. This book sets up the status quo for the book that is mostly intact over 80 issues later.
I'll accept suggestions for a better choice than Invincible #12. The rest are now locked in.
Son of Satan gets his own feature? First Doctor Light? First Gambler? First Thinker? First Blue Alien Starman? First Valiant Turok? Last issue of Secret Wars? Last issue of Camelot 3000? Last issue of Nextwave? Last issue of pick-a-maxi-series? Earth X, Inhumans, Punisher: Welcome Back Frank? There are a lot of choices to choose from)