The one directed at all four guys in "The Nerdvana Annihilation". It caused a Despair Event Horizon moment for Leonard.
(Penny comes in and is upset with the guys.)
Penny: OK! First of all, what you call a gap, was nearly 3 feet wide; I slipped and skinned my knee.
Leonard: Are you OK?
Penny: Azzzzzz! Second of all, the door to the stairway of the other building was locked, so I had to go down the fire-scape which ended on the third floor, forcing me to crawl through the window of a lovely Armenian family, who insisted I stay for lunch.
Leonard: That doesn't sound too bad?
Penny: It was eight courses of lamb and they tried to fix me up with their son.
Penny: Not done! By the time I finally got to work, they'd given my shift away. Yeah, that's right, I lost an entire day's pay thanks to this, this...
Sheldon: Time Machine.
(Penny stares at Sheldon, giving him an evil glare.)
Leonard: The lights flash and the dish spins, you wanna try it?
Penny: No! I don't wanna try it; my god, you are grown men, how can you waste your lives with these, stupid toys and costumes and comic books?! And now that! That...
Sheldon: Again, Time Machine.
Penny: Oh please! It's not a time machine, if anything, it looks like something that Elton John would drive through the Everglades.
Sheldon: It only moves in time. It would be worse than useless in a swamp.
Penny: Pathetic! ALL OF YOU! Completely pathetic! The one directed at Howard in "The Killer Robot Instability" caused a Heroic BSOD.
Penny: I know you think you’re some sort of smooth-talking ladies’ man, but the truth is, you are just pathetic and creepy.
Howard: Um, so what are you saying?
Penny: I am saying it is not a compliment to call me doable. It’s not sexy to stare at my ass and say, “Ooh, it must be jelly ’cause jam don’t shake like that.” And most important, we are not dancing a tango, we’re not to’ing and fro’ing. Nothing is ever going to happen between us. Ever.
Howard: Wait a minute. This isn't flirting, you're serious.
Penny: Flirting? You think I’m flirting with you? I am not flirting with you, no woman is ever gonna flirt with you, you're just gonna grow old and die alone.