For me, it is a toss up. I'm an old school gamer who adores a good boss fight and boss design. Since it was so early on in the game on my first playthrough, the first time I laid eyes on the Gaping Dragon I was stunned. I was literally fighting a giant dragon/vagina with teeth for labia. The fight itself was somewhat underwhelming, but the amount of wicked creativity that went into designing the vagina beast was awe-inspiring.
The second instance, which I'm sure is a popular one among PvEers, was the first time I beat O + S, by myself I might add. I of course thought it was wise to take out the Smough first, you know the big fat guy swinging a hammer might as well get rid of him first right? Little did I know how much easier the fight was to take out Ornstein first.
Curious to hear your thoughts!