Route 66 was on our route when we rode through the lower 48 in 2014. We did a lot of research for the trip in order to try and see all the interesting spots (even found dvds of a documentary on the route). Illinois had a lot of neat places to stop, but we quickly found that attempting to follow the exact route, and Route 66 was rerouted a few times during it's lifetime, was just about impossible.
In Illinois a lot of the "original" roads are still there and paved but riding them was just like riding across a giant washboard. Neither of our backs could handle the constant jarring even at slow speeds, so we ended up riding along the interstate and riding over to the original alignment to see the points of interest.
Then when we hit the southwest our main concern was the availability of fuel. Pulling a trailer and driving the gas hog (pre-heat fix) 2013 meant that I was very uncomfortable being on any stretch that might be over 110 miles between fuel stops. So in Arizona we stuck to I-40 when the original route cut off and we could not get any verification of reliable fuel along the route. Since then I have found better planning tools for fuel stops and we have had the heat recall so are getting better mpg.
We did add some off 66 excursions during our trip to include seeing family, making jogs to catch a state that didn't easily fit into the route any other way, POIs like the Grand Canyon, etc. IMO, the meeting point of the two theoretical groups of Spyders would meet well to the east of Adrian, TX if they were doing sightseeing along the trip. If you do go, make sure to take time in Adrian for the pie, it is excellent.
If you do have a bug to ride the road, there are some good resources out there. The dvd series we watched had some good information, the book Road Trip USA is an excellent resource with lots of details for many cross-country trips, and there are websites that do a good job of explaining the route. I still have the GPS files for our trip that I would be willing to share but you would have to do a bit of editing to remove any side trips.