For me exploring Vault 11 was definitely one of the most memorable. Putting together what happened (great story not related to an actual quest) and then opening up the tunnel in the Overseer's office. That last bit really got me good.
 
Also, at the end of the game should you go against the NCR...

Walking into the Legion Fort.
Surrendering all but the hold out weapons.
Insulting Caesar.
Killing him and his entire elite bodyguard with just the 9mm Maria.

• SPOILER WARNING: Click here to reveal hidden content.
• Accidentally letting the fellow into the Van Graffe's store and the resulting explosion 
• Bringing the B52 out of the lake
• Helping the Legion conquer New Vegas

Wiping out Cottonwood Cove and Fortification Hill with Boone.   Me and Boone, a couple of problem solvers.

• When Caesar has some kind of brain seizure and starts screaming in agony, and the failed Medicine check is something like "Does your head hurt?".
• The King explaining the history of his HQ.
• Yes Man.
  

The one that sticks out the most because I didn't expect it.

Finding out the House endgame mission and Yes Man endgame missions are basically identical. What a great moment, the game was telling me its done and none of the other endings are worth pursuing. Uninstall.

SPOILER WARNING: Click here to reveal hidden content.

New Vegas has been successfully removed from your computer.

At least it did that right.

Finding out the House endgame mission and Yes Man endgame missions are basically identical. What a great moment, the game was telling me its done and none of the other endings are worth pursuing. Uninstall.

• Vault 11.
• Enclave Vertibird dropping off the retired crew in Remnant Power Armor into battle.
• Seeing NCR Veterans for the first time.
• Boomers bombing the dam.

@Galiant: I didn't hate the game. The world isn't black and white, boy. 
Courting polar opposite adversaries only to find out the mission structure is identical is a bummer. And I found that out today. It doesn't mean I hate the game, retard. It just means the game's over.

The lesbian NCR sniper and No-Bark. No-Bark is a legend, I would subscribe to his newsletter if he had one. But then "they" would know what he knows about them.

" The lesbian NCR sniper and No-Bark. No-Bark is a legend, I would subscribe to his newsletter if he had one. But then "they" would know what he knows about them. "