Veidt: "Do it?" Dan, I'm not a Republic serial villain. Did you seriously think I'd explain my masterstroke if there was the slightest chance of you affecting its outcome? I did it thirty-five minutes ago.
Also while Nite Owl and Rorschach are looking through Ozymandias' office for clues about who might be targeting heroes, having been unable to speak with Ozymandias themselves.
Nite Owl: Rorschach, I think we're in bad trouble. The person behind this, the person we're up against... I think it's Adrian.
One Hundred Bullets #91: "Rothstein is dead. The connection is cut. No more attaches, no more revenge, no more hundred bullets. Graves' game is over."
Wolverine in X-Men 138: The Hellfire Club defeats the X-men, and Wolverine gets mass-increased until he crashes through the floor and winds up deep underground. He rises from the sewer, livid, and utters the line that changes him from secondary character into cult figure... "All right, suckers. You took your best shot. Now it's MY turn!"
Another Spider-Man example with a huge impact on the entire mythos and which comes as a revelation not just to the readers, but to the protagonist as well, from The Amazing Spider-Man #257:
Mary Jane: You don't have to make up another one of your phony excuses, Peter! Not now—! I know the truth! The real truth!
Peter: What are you talking about?
Mary Jane: I've known your secret for years! Up until now, I've always thought I could cope with it if I ever had to experience it firsthand — but I can't! I can't! I just can't cope with the fact that Peter Parker is secretly Spider-Man!
And then, of course, there's the two words that, if avoided, could have saved a storyline: "Do it.".
The first issue of the Joss Whedon run on Astonishing X-Men closes on a lecture that doesn't sound anything we haven't heard before, and then the last line turns it around completely: "They've been called angels and devils... they've committed atrocities, and been victim to atrocities themselves. They've been labeled monsters, and not without reason. But I will tell you what mutants are. Mutants are people. No better or worse by nature than anybody else. Just people. People with a disease. Mutants are not the next stage in human evolution. They are not the end of mankind. The mutant gene is nothing more than a disease. A corruption of healthy cellular activity. And now at last...we have found a cure."
A fairly mild example, as the announcement made in the final line was not something X-Men readers had not seen before, e. g. during the Kelly/Seagle run.
The Letter: "Mildred... didn't you hear? Saturday night Frances and Paul's car skidded in the rain and they hit a tree. John's still alive but Frances died instantly."
Baby Talk: "She's not there. Thelma took her to the clinic. They left an hour ago."
The Trial: "When Annie told me I should ask Jesus into my heart, I did!"
Ramona: (to Scott) Good job. Great. You actually made me think that you were a decent person. But you're just another evil ex waiting to happen, aren't you?
In book 6, when Scott talks to Kim about the past, and she reveals that he's only been a hero in his own mind, and is in fact a huge asshole:
Kim: Simon? The guy from high school? You beat the crap out of him and said we should date. He was 5 feet tall and didn't stand a chance.
War of the Green Lanterns: "Thaal Sinestro of Korugar. You have the ability to overcome great fear. You have been chosen. Welcome to the Green Lantern Corps."
Green Lantern #12: "Hal Jordan will become the greatest Black Lantern"
This one's especially painful. It was supposed to kick off a new story arc, but the series was cancelled prematurely, which caused it to be the last line in the series.
Flashpoint: "What did I do? Oh, Barry. My idol. My inspiration. That's the beauty of all this madness. I didn't do anything. Not a thing. You see, it turns out... You're the villain today."
Xavin: "Chase... ran away. I believe he had a disagreement with Nico about what to do with Gert's body."
Ultron: "Astounding. I anticipated your defeat of Doom, yet i was 99% certain you would be unable to damage him badly enough to uncover that he was merely one of my androids. Truly, you are my greatest creation."
Norman: He had not turned his back at us. He stands in the sky... faith rewarded. (vision of screaming Superman, which changes Norman's mood and reaction) ... dear God. The threat of Armageddon hasn't ended. It's just begun...
recording of Stryfe, as his base's self-destruct activates: Congratulations. You're human. For the next eight seconds.
My Little Pony Micro Series: Interestingly it wasn't "I'm Jade Singer" but rather Twilight's response of "I know." The story provides a neat twist on the typical "bitter old celebrity who has gone into seclusion" plot and plays with the Genre Savvy readers who can tell where the story is heading from early on.
Aquaman: "In a fit of rage, seeking revenge, Aquaman killed Black Manta's father.