My answer may seem a bit off but I'll try to support it:
With a natural sense of chemistry and the ability to go over the top and still very subtle, I'd have to go with:
Adam Sandler and Drew Barrymore (old comment also exposed)
I rented 50 First Dates strictly on the merits that I actually adored The Wedding Singer.
Now I have to admit I had a really low tolerance for Adam Sandler. Happy Gilmore, Waterboy, Big Daddy... couldn't stomach any of them. But with WS there's a balance that we see in Sandler's work. The balance comes from Drew Barrymore.
If it were just WS I could chock it up to Barrymore saving Sandler on screen. But the chemistry strikes a balance and they are able to find that point again in 50. Surprisingly with relatively different characters. I say relatively because it's still obviously Sandler and Barrymore. But to be honest, Spencer was always Spencer. But he slid into role after role very well.
So... Sandler/Barrymore. That's my pick for the next Tracy/Hepburn. :)