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.
MEREDITH: "You don't get to call me a whore. When I met you, I thought I had found the person that I was going to spend the rest of my life with. I was done! All the boys and all the bars and all the obvious daddy issues, who cares? I was done. You left me. You chose Addison. I'm all glued back together now. I make no apologies for how I chose to repair what you broke. You don't get to call me a whore." DEREK: "This thing with us is finished. It's over." MEREDITH: "Finally." DEREK: "Yeah, it's done." MEREDITH: "It is done."