Its not the focus of the game, rather its a very small part, but it has been done the absolute best in any video game I've ever played. The love between Jackie and Jenny in The Darkness was presented in a very real fashion that I could believe.
How has ICO not been listed yet.
No love for FemShep/Garrus? For shame. Absolutely support the Morrigan romance, one of the strongest female characters ever seen in a game. And Garrus can ...calibrate you.
Now, I doubt that anyone here played (or still remembers) Bulletstorm, but General Sarrano and the Protagonist have the best married couple dialogue.
I like Raynor and Kerrigan.
Anduin and Varian.
In all honesty though, probably Laharl and Flonne. He raided Heaven for the girl, that is pretty ballsy. (Disgaea)
Ryu and Ken.
Companion Cube.
SS Link and Zelda and Shadow of the Colossus. Those final moments in that game, after being shot and possesed by darkness, you still struggle towards the girl