And lo, there was much gnashing of teeth as Mass Effect 2 took its place as Game of the Generation. But it probably deserved it.
I'm playing Mass Effect 3 again right now, and much like my experience with the Matrix trilogy, I keep thinking about my fonder memories of the second as I trudge through the third's plotline. :P
The moment I liked best in ME2 is the collector's invasion of the Normandy, controlling Joker, while he (aka Seth Green) hobbles around muttering "shit shit..shit SHIT shit!!" Moments of complete terror and helplessness with Joker being the player's proxy. That really spoke to me as the game writers' moment being self-aware, coming full circle with an entire crew of characters that operate independently of The Shepard. We're gonna save the galaxy soon, but ohhhhhh this shit's going bad and no dialogue wheel will save it.
Not even my dear sweet Yeoman Kelly Chambers.