I think it's the eyes and the cheesy smile, but something about this is a little creepy in a good way. Listen to this [link] and look at this pic, it's awesomely funny when you do. Make sure you turn the volume down though, so you won't have a heart attack.
Reading the eyes, she is terrified. Heavily opened eyes (passed normal), the color palette being warm, and her looking over her shoulder gives the appearance that she is fleeing from an explosion or fire of some sort.
I would wager that is why you see it as 'a little creepy'.
Ohhhh. From the thumbnail I thought for a brief second that the part of her hair going in front of her face was actually supposed to be her mouth (as in a side view mouth wide open and seeing the hair going behind it).
I do love the style of this. It has its own different feel and I could see it hung on a wall like in a gallery! Actually, I think this my even be my favorite MLP art I've seen on DA so far. I'm not kidding! There is just something really special about the color choice and use of space and position...