We visited last spring and the ILs treated us to a package through the Grand Canyon Railroad - we drove from Phoenix up to Williams (AZ), stayed overnight at the Grand Canyon Railroad Hotel, took the sightseer train and then a highlights bus tour around the South Rim.
It's expensive, the included food is dreadful (I have nothing kind to say about the dinner or the lunch), and while the bus tour is cool some folks may feel a little rushed, so I'm not sure that's the "best" way to do it, but it was still 100% worth the trip.
I'd be open to hearing from other folks who did things differently.
If you decide to skip a tour group, and you have a 4th grader in your family, sign up for the Every Kid in a Park National Parks pass to get into the park. It runs every school year from September 1st through August 31st.
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Liz
DD (3/2010)
"Make mistakes! Get messy!" - Miss Frizzle