***Disclaimer: Violence is stupid and dangerous. A blow to the skull is often fatal.*** 

I wouldn't say it's easy, but there are several sweet spots on the skull that, when hit with sufficient force, is almost guaranteed to cause unconsciousness.

I would suggest the upper part of the jaw bone or the temple. Both places are connected to the brain stem through nerves and/or arteries. A punch here will cause the force to reach your brain and shut you down.

I also believe that it's an important factor whether you expect the punch or it lands like a lightning from a blue sky. The latter are by far the worst. You'll almost certainly wake up surrounded by panicked individuals with a severely swollen head and no clue as to what happened ... then you throw up.

Found this on [Quora](http://www.quora.com/How-does-one-render-another-unconscious-with-a-single-punch): 

> A bunch of studies of head injuries in primates were done at U Penn some years ago. Bottom line: it took 3 times less energy to knock an individual out with a ROTATIONAL blow (e.g. roundhouse punch) than with a TRANSLATIONAL strike (e.g. a jab).
> 
> There are 2 main mechanisms:
> 
> 1) Cerebrospinal fluid (CSF) can cushion a linear blow, but not a
> rotational one (the CSF and brain spin side by side in a rotational
> movement) 

> 2) the upper brainstem and higher brain can twist on each other
> because of their size, shape and relative positions (and the arteries
> that supply them can also twist), kind of like an apple and its stem,
> causing loss of function precisely where "consciousness" resides in
> the brain (the reticular activating system)

The studies mentioned by the Quora poster might be any of the [many studies](http://www.seas.upenn.edu/~injury/Publications.html#Head) that came out of the Head Injury Laboratory at the University of Pennsylvania, but is most likely referring (primarily) to "[Physical model simulations of brain injury in the primate](http://www.ncbi.nlm.nih.gov/pubmed/2384494)", by Margulies SS, Thibault LE, and Gennarelli TA (published in the Journal of Biomechanics in 1990).