Just did the I-80 NE route last Friday/Saturday. Also have done the I-70 KS route a few times. Either one will give you long lonly streches.
Your biggest consideration should be getting across the Rockies while in CO.
If taking 80, cut over on I-76 to Denver and take I-25 down to CO Rt. 160.
If taking 70, cut over on CO Rt. 24 in Limon to go to CO Springs. Then take I-25 down to CO Rt. 160.
CO Rt. 160 gives you a pretty good ride into Durango and Mesa Verde. We took this route last summer (stop at Great Sand Dunes NP if you get a chance) on our way to Mesa Verde.
Mesa Verde NP only allows you one guided tour per day. We did Cliff Palace and Balcony House on our first visit in 2001 and did Long House and Mug House last summer. Mug House does not look to be open for tours this summer. They have Oak Tree house open instead:
Oak Tree House and Fire Temple
A moderately strenuous 2-hour, 1-mile (1.6 km) round-trip hike. Includes walking along cliff edges, climbing a 15-foot (4.6 m)ladder and hiking a narrow dirt path to visit two cliff dwellings. Hikers will also get to see a unique plaster panel that is undergoing preservation treatment.
Very nice campground in the park with hook ups. Great food at the Metate Room.