Saren:
He is the main villian in the game. He is the most valuable, effective and longest serving Spectre which is considered the right hand of the council(Galaxy's government). They are allowed to use anyway necessary to complete their missions and Saren is the most ruthless. Hugo Weaving is the only choice for this villian he is very menacing onscreen and he also has that commanding voice that matches Saren's.
Matriarch Benezia:
She is a very powerful biotic and also the mother of Liara T'soni. The title Matriarch is given to spiritual leaders of the Asari. She is Saren's second in command. Holly Marie Combs is a good choice in my opinion....she can play a sophisticated figurehead like Benezia is and she can also do action pretty good. She also has the look down.
Sovereign:
This gigantic synthetic is part of an A.I. race known as the Reapers. The Reapers destroyed the protheans about 50,000 years before the time of the game.
He sees no use of organic beings and is very very intimidating and unknown.
I think that he should be all CGI with Peter Jessops voice(voiced him in the game).
Well there you go. I'll probably do a supporting characters cast in a little while. Enjoy....let me know what you think in the comments.
(I got my pictures from google.com)