All six have their ups and downs but if I had to choose one, it will be Pinkie Pie, no offensive of course.
While she can be hilarious at times, she can also be very annoying at times, such as in "A Friend in Deed". I get that Pinkie Pie didn't have any bad intentions of course, but it was just downright annoying that she wasn't able to pick up on the fact that Cranky didn't want to talk, even following him to his house and finally getting the picture after he kicks her out of his house. At least she was able to reunite him with Matilda.