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Mass Effect 2
Fan Nickname: The game that gave birth to Garrus being called Space!Batman.
Hey, It's That Voice!: Tons!
Meme Acknowledgment: BioWare merchandising produced shirts for the "Sir Isaac Newton is the deadliest sonofabitch in space!" and "I'm Commander Shepard, and this is my favorite store on the Citadel" memes.
Playing Against Type:
Martin Sheen as the Illusive Man.
Carrie-Anne Moss as Aria.
Though... acting cool and sarcastic in a nightclub while she waits around for Our Hero? Not much of a stretch.
Kal'Reegar is a much more open-minded, upstanding character than some of Adam Baldwin's more notable roles, standing in sharp contrast to Chuck and his parts in the Whedon universe.
Relationship Voice Actor:
Sure, Why Not?: BioWare's response to Garrus' and Tali's popularity and the fans' desire to have them romance options. Garrus even addresses this trope when Shepard shows interest in him.
What Could Have Been:
Cut content from the Firewalker DLC reveals that one of the scientists you're trying to find was a minor NPC from the first game on Eden Prime, the one who was "raving".
At one point it was possible for Miranda to be romance by a Fem Shep.