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Mass Effect 2 is unquestionably the best entry, but the first game is still my favorite. It's got a stronger core narrative, more RPG mechanics, and just does such a fantastic job establishing the whole ME universe. You get introduced to all these different things without it ever feeling overwhelming or like it's just a nonstop exposition dump. The fact that they managed to so seamlessly establish that many different compelling species, social and political dynamics between them, technology, etc...it's just fantastic. I'll never forget what it was like playing that game for the first time.

I prefer playing as FemShep. They're both great, but Jennifer Hale really kills it with the delivery to the point of perfection.