Finally had a chance to take a closer look at the map. It looks like I could take I-285 to I-160, cutting through Durango and all the way to the Grand Canyons. That might be perfect, and of coruse vice versa if I go from the Canyons to Colorado instead. Since it's not a major interstate I wasn't sure how good the road conditions or traffic would be. Thanks for the cotrip link!
I'm shooting for last week of September and the first weeks of October so I'm there when fall foliage is in full bloom. Should make for some breathtaking drives and scenery.