I remember a friend of mine bragging (in jest, not in seriousness) about how much sex he’d gotten earlier in the day. After a minute or two, he dropped the phrase sexual exhaustion, which opened me up for “Sexual exhaustion, huh? Try your other hand.”
Great stuff here! (Thought I’d better pop up in my own thread again …) These are some good stories 
when I worked as a cop, a routine traffic stop. I asked the driver “Do you know why I stopped you?” Her response was “Gee officer I thought for sure you would know!” That has happenned to so many rookie cops it is almost urban legend.
My example isn’t very good, but I just love shutting up cocky freshman at my school. A few weeks ago, I was going to buy a bottle of water from the snack machine, but it was sold out of water and I said something like “Ah man there’s no water left…” This freshman behind me said “Who drinks water? No one drinks water.” And I responded, “Well obviously people drink water if it’s sold out.”
Not too witty but nevertheless an incredibly satisfying “no shit, you dumbass” moment.
Reily: “The ocean called, they’re running out of shrimp”
George: “Well the jerk store called, they’re running out of you”
George: “I had sex with your wife.”
Chairman: (To George): “His wife’s in a coma…”
My great shut-up story happened one morning during first period English Comp 2 in High School.
My teacher had called me up to her podium to give me some work I had done.
Apparently, the zipper on my jeans had failed that morning, because I heard my friends Andrew and Clay whispering about it while I was up at the podium (the classes in my high school were very small… the biggest classrooms had 20 desks. My graduating class had 45, so everybody knew everybody).
Having heard this, I turned around and started walking back to my desk, right behind the two. Courtney sat near us also. Now Andrew, Clay, and I always joked around with everyone, and Courtney thought this would be the perfect time to match wits with me.
Courtney, having heard Andrew and Clay whispering about it, calls me out before I get to my desk, and says, “Hey, your fly is open!”
Somehow, I manage to retort, with perfect timing, “Damn it Courtney, I told you to zip it up when you were done”
The class promptly erupted in laughter.
Even our english teacher laughed a little.
Mine wasn’t so much funny as it was a blessed relief to finally get a little quiet.
I was taking a ceramics course to beef up my CEUs. There was a woman in there who was loud, obnoxious, mean, and thought she was clever. All class period long, we got to listen to why the teacher didn’t know what she was talking about, why her stuff was going to be so much better than ours, blah blah blah.
I should have spoken up earlier, but I had work to do, so I kept my head down and focused on that. During the last two class periods, we did critiques. All of us put out our finished works in a pleasant arrangement, and we went around one by one and evaluated them. Little Miss Snide is making comments just loud enough for the student being critiqued to hear. All her comments were mean, petty, and intended to be funny but just fell flat on their faces. She never got that none of us were laughing.
Finally, I said, “your comments are distracting and hurtful. Please stop.”
“I’m only telling the truth,” she protested.
“Yes, but think of all the truthful things we could say about you if we wanted to,” I answered.
She did not utter another word after that.
Opinionated Blowhard: “Well, you know what I think…”
Me: (cutting him off) “Karl, I am monumentally unconcerned with what you think!”
I remembered this one tonight as a good one for this thread. I was living in a rooming house when one of the least favorite tenants was being evicted. On her last day, she was still scrambling to find new digs, and the Landlord had told the on site manager to put her stuff on the lawn, as she was making no moves to vacate her room. A friend of hers she had left to ‘guard’ her stuff kept telling us “You can’t do that, it’s illegal!” etc. I stopped and asked him. “Which Arizona Revised Statute or City Code are we violating, exactly?” He stopped, and sputtered a bit. “Well, I’m not a Cop, or a Lawyer…”
“Then you probably shouldn’t be telling people what’s Illegal.”
It shut him up, anyway.
Not exactly a “shut up” line per se, but I always thought that dealing with difficult customers a case of mind over matter, as in - I don’t mind, and they don’t matter - didn’t go over terribly well when I told a customer this though…
Here are two I’ve used.
Other person: I hate to say this…
Me (interrupting): Then don’t.
One day, two friends and I were talking outside our classroom. Another classmate, whom none of us liked at all, was writing on some colored paper. When she finished writing them, she interrupted one of my friends by saying, “I just finished two letters.” Nobody said anything until I looked at the unliked classmate and said, “Really? D and E?”
Oh, how could I have forgotten my favorite one? When living in California, I loved to do the following to certain Texans who were braggarts.
Them: (Some comment about cowboy life or Texas stuff)
Me: Wow. You seem to really like that tough cowboy stuff. Where are you from?
Them: I’m from Texas!
Me: Oh, back East, huh?
Heh, as a Texan, I gotta say, that’d certainly give me a moment’s pause. That said, when I think of California, the only time I think of anything quite close to a western is Zorro. 
When my dad was in the Marines, he was in basic training with a guy from Minnesota. The Minnesotan was going on and on one day about how many lakes there were back home. “It’s the Land of 10,000 Lakes, yadda yadda yadda!”
My dad, from Washington (state) finally said, “Big deal. In Washington, when we want a lake, we put one in. In fact, they’re putting in a lake behind my house right now!”
He was referring, of course, to the number of dams in Washington. At the time (early 60’s) they were building a dam on the river near the house my dad grew up in. And when he got out of the Marines, he came back home and got a job working on another dam
Aww shucks. Thank you kindly.