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.
Did you say it? 'I love you. I don't ever want to live without you. You changed my life.' Did you say it? Make a plan. Set a goal. Work toward it, but every now and then, look around; Drink it in 'cause this is it. It might all be gone tomorrow."
Arizona: Oh my God! I mean, I understand why you're into her. She's hot. Wait, she likes you? Nathan: What? I mean, I'm going to try not to be offended at that. Arizona: No, no, no. It's just that Derek was--Derek was epic for her. They were the great love story. I mean, that girl's heart beat for Derek Shepherd. It just...it never occurred to me that she would ever be with anyone else. He was perfect. He was everything. That man turned her world. It...I spooked you. Don't be spooked.