It took them quite some time to get together, but once they did, their relationship was incredible. Alex stood by Izzie's side as she battled cancer, and they had a beautiful wedding. It's enough to melt anyone's heart. But then, Izzie suddenly left, and Alex was stuck with her medical bills.
Perhaps if the actress who played Izzie, Katherine Heigl, hadn't decided to exit the show, the romance wouldn't have ended quite so abruptly.
And if Justin Chambers, the actor who played Karev, hadn't exited the show years later during season 16, he may not have hastily been written off as leaving Seattle to go be with Izzie, who had apparently had twins using his sperm.