From the show itself:
John Winchester: All right, if I'm not back Sunday night?
Young Dean: Call Pastor Jim.
John Winchester: Lock the doors and windows, close the shades, and most important...
Young Dean: Watch out for Sammy.
Michael: You said you're a big brother.
Michael: You take care of your little brother? You'd do... anything for him?
Dean: [heartfelt] Yeah, I would.
Michael: My brother's sick.
Dean: The little guy?
Michael: [nodding] Pneumonia. He's in the hospital. It's my fault.
Dean: Ah, c'mon, how?
Michael: I should've made sure the window was latched. He wouldn't have gotten pneumonia if the window was latched.
Dean: Listen to me. I can promise you, that this is not your fault. Okay?
Michael: It's my job to look after him.
— Why this show could be the codifier for Big Brother Instinct, "Something Wicked"
Sam: "AC/DC? Sabbath? Metallica? It's like 'The Greatest Hits of Mullet Rock.'"
Dean: "House rules, Sammy—driver picks the music, shotgun shuts his cakehole."
— Supernatural, "Pilot"
"I hope your apple pie is freakin' worth it!!"
— Dean Winchester, "Scarecrow"
"Your dad? He's in here with me - trapped inside his own meat suit. He says "hi"¯, by the way. He's gonna tear you apart. He's gonna taste the iron in your blood."
— Azazel-as-John, "Devil's Trap"
"I full-on Swayze'd that mother!"
— Dean Winchester, "In My Time of Dying"
"WWBD: What Would Buffy Do?"
— Ed Zenkman, "Hell House"
"Why do we have to sacrifice everything, Dad? Why do I have to be some kind of hero?"
— Dean Winchester, "What Is and What Should Never Be"
"This isn't funny, Dean. The voice says I'm almost out of minutes."
— Castiel learning how to use a cell phone, "The End"
Sam: Why? Why tell us anything?
(Demon) Crowley: [pointing the Colt at Dean] I want you, to take this thing to Lucifer, and empty it into his face.
Dean: Uh-huh. Okay, and why, exactly would you want the Devil dead?
Crowley: [putting the Colt down] It's called survival. But I forgot, you two at best are functional morons.
Dean: Yeah, you're functioning morons...
— "Abandon All Hope"
Lucifer: They are broken! Flawed! Abortions!
Gabriel: Damn right they’re flawed. But a lot of them try. To do better. To forgive. And you should see the spearmint rhino.
— Gabriel delivers his CMOA to his big brother Lucifer, "Hammer Of The Gods"
Castiel falls prey to Famine's powers, and his host body's desire for red meat
"What are you, the Hamburglar?"
— Dean, "My Bloody Valentine"
Andy: You get visions... of people about to die? [Sam nods] ... That's impossible.
Sam: A lot of people would say the same thing about what you do.
Andy: [pause] But death visions? Dude, that sucks.
— "Simon Said"
Dean: REO Speedwagon?
Jo: Damn right, REO. Kevin Cronin sings it from the heart.
Dean: [smirking] He sings it from the hair. There's a difference.
Castiel (staring at the t.v.): It's very complex. If the pizza man truly loves this babysitter (Sam and Dean look from up their work) why does he keep slapping her rear? Perhaps she's done something wrong?
Dean: You're watching porn? Why?
Castiel (still staring): It was there.
Dean: You don't watch porn in a room full of dudes, and you don't...talk about it! Just turn it off. (Castiel looks down at his body, surprised) Oh, now he's got a boner.
Samuel: This what you boys do, sit around watching pornos with angels?
Castiel (deadpan, eyes still glued to the screen): We're not supposed to talk about it.
Crowley: Ah, Castiel. Angel of Thursday. Just not your day, is it?
Castiel: What are you doing here?
Crowley: I want to help you help me help ourselves.
Castiel: Speak plain.
Crowley: I want to discuss a simple business transaction, that's all.
Castiel: You want to make a deal? With me? I'm an angel, you ass. Don't have a soul to sell.
— "The Man Who Would Be King"
Castiel: I'm going to find God.
Castiel: yes. He's not in heaven; he has to be somewhere.
Dean: Try New Mexico, I hear he's on a tortilla.
Castiel: (deadpan, looking slightly confused) No, he's not on any flatbread.
— "Good God, Y'all"
Dean: Sam, I'm sorry for psychologically scarring you.
Sam: Which time?
— "Plucky Pennywhistle's Magical Menagerie"
Detective: Gotta ask...do you boys chase the crazy, or does the crazy chase you?
Sam: Depends on the day.
— "Hunteri Heroici"
Dean: What are we doing?Describing the show:
Sam: We're hunting a ghost.
Dean: A ghost, exactly. Who does that?
Dean: Us, right. And that, Sam—that is exactly why our lives suck. I mean, c'mon, we hunt monsters! What the hell? I mean, normal people, they see a monster and they run. But not us—no, no, no, we...we search out things that want to kill us! Yeah, huh? Or eat us! You know who does that? Crazy people! We...are insane!
— "Yellow Fever"
"the demon-killing brothers"
"that reality show about the two underwear-model brothers who hallucinate and shoot at ghosts"
"the reality show about the two brothers who drive around testing out seedy motels"
"the underwear-model-ghost hunters-brothers show"
- Misha Collins, via twitter
Question: What is Hollywood likely to do to Supernatural if some 'creative genius' doesn't reign it in?
Misha Collins: Honestly? I'm just going to answer this quickly to get it over with, but ...gay porn incest story with two brothers fucking the shit out of each other.