When I ran up to the bridge of the Normandy SR-1 at the beginning of Mass Effect 2 and saw the giant hole the Collectors had ripped in my ship. I knew that the Normandy was going to blow, I knew Shepard was going to die, but that moment hit it home for me. I recall that when I saw it, I couldn't help but say "There's a hole in my ship." I was too stunned to say much else.
There were many, many moments afterwords in ME2 that also stunned me. Every single character is unique and impacted me in their own way. The romance scenes especially, some of those were heart-rending and sweet in an indescribable way.