The only thing I disliked about Anders hitting on me was that I was forced to sound so harsh and judgmental in order to reject him. Would have been nice if I could have said something along the lines of "I'm flattered, but not interested."
I think SWTOR does pretty good with this.
Since SirGladiator mentioned Doc, I'll use him as an example. From what I've seen, there's a 'nice' way to turn him down or a 'not so nice' way. While both may net you negative affection, there is an option to not sound harsh about it.