Given that Sherlock's reputation is for being "married to his work" and John's is "John 'Three continents' Watson," (and also he's supposedly not as brilliant as Sherlock) wouldn't you think someone who deals in seduction, like Irene does, would try her charms on JOHN (and therefore, undermine Sherlock through John, the way other villains do)?

She could even play on John's seeming need to prove he's still hetero.

The obvious answer is, she finds Sherlock more attractive and interesting, but that would mean she is really motivated by attraction and NOT just playing games.

Or, is it that, for all Sherlock's brilliance, his inexperience in human relations makes him a better target for Irene's particular brand of manipulation? 

I would think even a man who has been with women on three continents would find Irene...out there...to say the least, but maybe John's experience in that arena means he's less likely to be impressed by charms like hers?