The Big Bang Theory -- it's the TV show referenced in the prompt title; two of the main characters are Sheldon, a geeky (and seemingly asexual) (and extremely socially awkward) physicist, and Penny is his blond-bombshell (yet girl-next-door-type) (also a bit ditzy) neighbour (and aspiring actress/currently a waitress).

Sorry...I am having too much fun with parentheses this morning. Anyway, the joke is that Penny actually has a brief relationship with Sheldon's roommate, Leonard, who is also a physicist and a little less awkward. The point being that anybody who was rooting for Sheldon/Penny can only take recourse to fanfiction.

And I know all this not from watching the show, but because it's written about in places that talk about other shows. Yes.