In the annals of television comedy, some pairings are simply classic to the point of everlasting. I thus posit that the partnership of Leonard and Sheldon has already made that list (although Sheldon might point out that it would be more proper to call the team Cooper and Hofstadter, because traditionally comic pairings are known by their last names, the listing would be alphabetical, and -- most importantly -- it would list him first).
However, to simply reduce THE BIG BANG THEORY to nerdy roommates Leonard and Sheldon (Johnny Galecki and Jim Parsons) would be grossly unfair, because the show's success is due to its ensemble nature. The science squad would be woefully incomplete without the acerbic man-child Howard Wolowitz (Simon Helberg) and innocently naive Raj Koothrappali (Kunal Nayyar).