Gotta say Keanu and Sandra in Speed, and then The LakeHouse. I don't really know how to describe chemistry, or say who hasn't got it.. or who hasn't, but they just click. They just make me smile whether it be a funny scene, or a sad scene because they're SO good at what they do!
And then there's Noah and Allie in the Notebook, *big sigh* again, can't describe the chemistry but that was magical..