I'm going to take a moment to argue for
Brothers: A Tale of Two Sons, because this contest came down to some absolutely monstrous choices and it's gonna struggle from reflex votes.
I want to start by explicitly removing Portal from this argument, as I think it's the other main contender for the crown, at least in terms of my original intent with the poll.
Keeping it simple and universal (and critically, spoiler-free), Brothers managed to gut me emotionally using techniques unavailable to traditional media. The crux of this was the control scheme which, after three hours (preferably in one sitting) of gentle repetition and conditioning, became the lynchpin to the entire thing. I need to be vague here, but the story paired with the control scheme culminated in a finale that broke my heart so significantly, I can't think of a match outside of the personal losses inherent to 40 years of real life.
To this day, Brothers is a scar on my heart, and it's almost entirely due to some really smart considerations about how we physically interact with our stories. I'm thrilled it came this far, let's give it its due and our votes.
Editing to add: My brief argument
against the other (excellent, worthy) games—Portal aside, is that they were largely inventions. The ones that weren't inventions should have never made it here.