The only couple on this list who actually hooked up prior to the series ever starting, Grey's Anatomy kicked off the morning after Meredith and Derek went home from a bar together. Sure, he was married at the time - but that technicality was no match in the end for (sorry we have to say it...) the McDreamiest pairing on all of television.
Derek: I am calling post-it, Zola, Bailey, the tumors on the wall, ferryboat scrub caps. I thought D.C. was everything. I was wrong. You... you're everything. I love you and I'm not going to stop loving you. I can't live without you. I don't want to live without you, and I'm going to do everything in my power to prove it. Meredith: I can live without you, but I don't want to. I don't ever want to.