Full Fist
Not sure if it helps or if i will subject myself to ridicule, but my personal experience is to aim to hit with the ENTIRE fist. As in all 8 knuckles. The fist is tense in such a way as to be square, not so tense as to make the first two knuckles protrude. When you punch in this way the middle knuckle is largest and will take the brunt of the impact.
Hitting CURVED BONE such as the face causes ones hand to slip, I defy anyone in the heat of the moment to aim accurately using a specific knuckle. Concentrate on keeping a solid shape with the wrist and fist is good enough.
Try Wrapping a BOWLING BALL in rags, then punch it. You will see the difference in punching a skull when compared to punching a bag. Plus you have to take into account the speed and ease of movement of a persons head.
Stabbing someone in the face with a knife will not knock them out. Hitting with one knuckle would cause a lot of pain, but generally i think a dizzying blunt attack would be preferable. Unless off course you are more intent on mutilation than simply defending yourself.