My initial response is that even for anime facial structure, the cheekbone on the left is far far too low, and at the very least does not seem to match up with the cheekbone on the opposite side of the face (as indicated by the light/shadow). Also, based on my (extremely slapdash) edit, the eyes may be off-center. Lastly, I would reckon that you could lose some colors, although I myself am not particularly obsessed with low color counts.

From a content point-of-view, the facial expression is very creepy/generic anime. Yes I understand that he is a fun-loving and golden-hearted youthful ne'er-do-well, or something, but I think the style carries that baggage and not the facial expression, if you follow. A portrait is an opportunity for the character to interact with the viewer as a person, (not necessarily by staring directly at them, mind.) Here he seems to be the victim of those unfortunate photographs taken of people mid-word.

Finally, this person has 3 'sides' of the whites of his eyes showing. Look at the link below for a highly unscientific explanation to why this may be a concern.

http://www.octogenariansblog.com/san-paku-three-sides-of-white-showing-in-the-eyes/

All that said, there is much to like in this picture, and I hope my nitpicking is helpful.