This Take was spurred on when I realized that an actor I like was in one of my favorite games of all time, Fallout New Vegas, not after recognizing him during the well over 300 hours I'd sunk into the game, but after reading the Wikipedia page for it so here we go.
Danny Trejo as Raul the Ghoul Companion in Fallout New Vegas
This is where this all came from. It took me a trip to Wikipedia to realize that Danny Trejo voices Raul the Vigilante/Cowboy/Mechanic/Ghoul Companion. Now this one is more known that some of the others here.
Susan Sarandon as Granny Rags in Dishonored
You might know Susan Sarandon from movies like Thelma and Louise but you probably didn't recognize her as the cannibalistic yet not hostile witch Granny Rags in Dishonored, who is at war with the Gangster Slackjaw. Now the Developer wanted to make her be the kind of villain that you'd like but most people (myself included) like Slackjaw better, to the point where you have to choose to either help kill a tied up Slackjaw or free him and ice Granny Rags. Most people stab Granny Rags in the neck (myself included).
Lance Henrikson as Admiral Hackett in the Mass Effect Series
I only learned this recently but Admiral Hackett is voiced by the actor Lance Henrikson, who had notable roles like Bishop in the Aliens franchise.
Samuel L. Jackson as Officer Frank Tenpenny in GTA San Andreas
Samuel Jackson plays the Antagonist of GTA San Andreas who really is set up as worse than your character but considering how most GTA players play, he's probably a saint compared to you.
Astronaut Buzz Aldrin voices the Stargazer at the end of Mass Effect 3
Yeah, that guy at the end who is in the bonus scene after the credits is Buzz Aldrin. Which, correct me if I'm wrong, but I'm pretty sure makes this the only science-fiction video game whose cast includes a guy who actually went to space, let alone set foot on the goddamn moon.