My family moved to California from Kansas in 1960 for my father to work in the oil fields. When we returned to Springfield, Missouri in 1962 we took Route 66 all the way (no interstates yet). Us kids loved it. My mother told me that she enjoyed the trip on 66 as well. Not on a motorcycle but enjoyed it never the less.
Since then, I have ridden all of the parts of it that remains (and I could find) from Springfield, Mo west on my bike once. Well worth the experience. I don't know about doing it in one weekend, I would think that this is something to take your time doing to get the feel for it.
Namaste'
Doug in Kentucky