I remember going to a friend's house and sitting in front of the TV. He hands me the xbox controller and tells me "You are gonna love this game". I spent the next 2 hours completely consumed in the game. As a sci-fin fan, this was the kind of game I had only dreamt of. It felt a bit Star Trek, a bit Star Wars, a bit Babylon 5 and with elements from so many other stories, but somehow, it felt truly unique. The trilogy had some low points, many of them in MS3, but I was one of the rare cases that enjoyed the original ending, it felt so appropriate and a subeversion of expectations. I also enjoyed the added endings.
Many games have tried to get close to its charm, but in my book, no sci fi story in video games is better than the story of my Commander Shepard.