As a native, I have a hard time saying what's the most difficult aspect to master, but from this forum, I can tell you that it seems the most difficult concept for English learners is which prepositions to use. It seems completely arbitrary, and even among the natives, there is disagreement on things like "opinion about"/ "opinion of" and (one that puzzled me as to the depths of the emotion it caused) "stand in line" / "stand on line."

Based on what I hear around me, natives still have trouble with the possessive before gerunds "I appreciate you coming on such short notice" when it should be "I appreciate your coming..."  Also, whom is a source of confusion. People don't use it when they should and use it when they shouldn't.

And my personal favorite, which I have blogged on, is when Americans (maybe Brits do this too) won't use "me" when "me" is the right word, proabably because they were corrected as children everytime they said "so-and-so and me did something" - so you have awful things in business writing like "Contact Mike or myself with any questions" or "Between you and I, I think we'll get the price we're asking for."