Whew. This could've been awkward.
Aniston was named favorite female star, while Vaughn was picked by the public as favorite leading man.
"You all have supported me since the days of Friends," Aniston told the audience, "just through all of it â€" good work, bad work and the ugly. I just thank you."
Aniston also poked a little fun at Britney Spears, quipping about the short skirt she was wearing: "Man, I tell you, it's a lucky thing we do wear underwear, huh?"
Among other winners, Johnny Depp, who was filming in London and unable to attend the ceremony, accepted his favorite male movie star and male action star for Pirates of the Caribbean: Dead Man's Chest via satellite.
He and costar Keira Knightley were also selected favorite onscreen match-up.
"Thank you for a second chance!" Dempsey told the crowd. "I'm very fortunate to be part of a great ensemble." To the show's creator, Shonda Rhimes, he said: "Thank you for creating Dr. McDreamy, it's changed my life."
And Desperate Housewives's Eva Longoria, who was named favorite female TV star, told the crowd: "If it wasn't for the people, I'd never win an award."