Boy, I wish the best moment was the end of ME3 and the conclusion of the epic story, but alas, it was not to be.
Honestly, the high point emotionally for me was just before the solo Reaper boss fight in ME3 (I forget what planet it occurs on). See, back in ME1 I wanted (or should I say, Sheperd wanted) to romance Tali so badly, but settled for Liara. He stuck with Liara throughout ME2. But when Tali was available in ME3, Shepard dropped Liara like a bad habit and hooked up with Tali.
So their relationship was a long time coming. And just before going out on a nearly impossible task of defeating a Reaper singlehandedly, Tali says “I love you” and Shepard responds with “Keelah se’lai”. I’ll always remember that.
On my first playthrough, my Shepard made all his decisions for Tali’s benefit. I had avoided spoilers so when I got to the final decision, I had no idea which was considered “best”. Shepard didn’t like the idea of the “symbiosis” because it might change Tali, so he picked Destruction.
