Let me just say, at the outset, that I think the cast and writers for the Mass Effect series have all done a brilliant job, so this list is just degrees of excellence. However...
THE VERY GOOD:
Adam Baldwin did a great turn as Kal'Reegar, managing to make him so much more of a character than the writing provided.
Michael Beattie's Mordin was priceless, as was the script for him.
Keith David breathed both warmth and melancholy into Anderson. He owns him now.
D.C. Douglas managed to make a believable robot. Granted Legion was also well written, but still.
Seth Green, brilliant as ever. A joker playing Joker.
I'm in the Jennifer Hale-as-Shepard camp. It's not that Mark Meer is appalling, it's just he never sounds like he's trying. Hale's passion for her work shines through every line.
Michael Hogan (Bailey) and Tricia Helfer (EDI) - who, of course, knew the ropes from Tiberium Wars - were great, and I'm glad that Galactica is getting it's due, along with Star Trek (Michael Dorn (Uvenek), Marina Sirtis (Benezia)) and Farscape (Claudia Black (Daro'Xen)). Grace Park, James Callis and Edward James Olmos for ME3? Also, Robin Sachs (Buffy, Babylon 5, Galaxy Quest, Star Trek: Voyager) as Zaeed, clearly felt at home.
Brandon Keener's Garrus is utterly convincing, and one of the best things about Mass Effect. Ditto for Liz Sroka's Tali.
Adam Lazarre-White got Jacob off the page well.
Courtenay Taylor deserves a special mention for putting some real grit behind Jack.
Peter Jessop is brilliant, too. Seriously, Mordin's traitorous pal was also Sovereign and Lorik Qui'in?
Raphael Sbarge (Kaidan), sexy as ever.
Lance Henriksen (Hackett) and Martin Sheen (TIM) don't know how to do bad.
And let us not forget Neil Ross as the Codex narrator.
For me, though, hearing Martin Jarvis during Tali's loyalty mission was the standout moment. I thought Shohreh Aghdashloo was going to be the thing there, but as a Brit and a Dr. Who fan, Jarvis was the win.
THE NOT-SO GOOD:
I was sorta half-expecting Carrie-Anne Moss to do better, but alas I think she's very much a screen actress. I never quite believed Aria.
I'm not sure what happened to Miranda. Perhaps it's the face leaping out from the others (too surreal), because Yvonne Strahovski wasn't too bad. Maybe I just didn't like the writing or the character. She's the ME2 game icon, though.
Kimberly Brooks has never done anything for me as Ashley.
Ali Hillis was perfectly fine as Liara in the original game, but just can't quite pull off where the character is in the sequel.