The Defenders. I love The Defenders. They started off weird and then got even weirder. When you put The Hulk, Dr. Strange, Namor and The Silver Surfer on the same team (excuse me, non-team) you really don't have to try too hard to find the bizarre situations. I mentioned this cover a couple of years ago and I'd put it on this list but it was from Marvel Feature and I'm sticking to actual Defenders covers here.
Unlike many other comic covers (e.g. Fantastic Four) this one depicts the antagonist at ACTUAL SIZE! Also, the text on the cover is not hyperbole even though it's a little inaccurate. He's a big computer-monster dude and all he has to do is say his creator's name to begin DESTROYING THE EARTH!!!! ZOMG!
I hear Microsoft security has to go through the same thing with Steve Ballmer at least once a quarter.
I really like the depictions of the ghosts on this one. The narrow palette and the Gargoyle's creepy-ass face in the corner top it off. Plus, Ten Speed Bike!!!
That's Eternity the Defenders are hanging out with. He's the personification of our universe. This is the scale of story the Defenders often found themselves in. I love, Love, LOVE the lettering on the title. It's reminiscent of Eisner and Steranko.