This is an important topic and I'm glad you started this thread. The headphones should be vertically higher up on your ears than lower. Front to back your ears should be positioned in the middle of the earcup. You can also move the headphones a little more forward so that the earcup is close to the back of your ear, and see if you like the way it sounds. On my crooked head I find the best position is the way I described above, and with the headband adjusted to the 6th notch down on the left side and 5th notch down on the right side. Since all of our ears are not perfectly symmetrical in placement, you may have to have one earcup slightly off-centered from the other earcup.
You will know the perfect placement when the soundstage becomes startlingly accurate. If the recording is good, vocals should be dead center and every detail of voice and instrument should be clearly focused with a well-defined image. The slightest imbalance in proper positioning on the head will blur the center image detail.
For me, this position puts a little more pressure on the back of my head than it does when they are directly centered over the ear. I find it to be a minor trade-off in comfort for the best sound quality.
The most comfortable position is to tilt the headphones at an angle, with the headband laying on top of your head but more towards the rear, as horribly illustrated below. The representation is if I were viewing your head from the side.
Top of head
[size=xx-large] \[/size] Nose
But this does not yield the best sound quality. It does sound good with some music though.