Technically speaking, it'd have to be Portal or Half-Life, or even Ace Combat Zero, since Namco/Bandai is independent.
However, my favorite game developed and published by a small studio would have to be Defcon by Introversion Software. It's a really fun game about global thermonuclear war. Yes, I really just said that: it's a really fun game about global thermonuclear war. The object isn't so much to win but to lose the least compared to the rest of the world. I really wish Introversion would show some more progress on Subversion: that game looks really sweet too.
I also just finished the story in a really cool Freelancer/Wing Commander Privateer like game called Galaxy on Fire 2 for the iPad. The space combat mechanics could use a bit of improvement, but overall, it was really cool. It's kind of a dying genre.