We're visiting in July, plan to leave Vail mid morning and have 3 days to reach Durango. Thinking about overnight stops in Salida and Ouray. How long would that route take us to drive ( minus stops to enjoy the scenery)? Any suggestions for sight seeing & motels along the route? Definitely want to see Mesa Verde, is Durango a good overnight from there?

You can get to Durango in a day but I would definitely suggest you stay in Ouray at least one night. Something big there is renting Jeeps and driving the old mining trails. Ouray also has a large swimming pool that is actually one big hot tub!

Give yourself a day to ride the train from Durango to Silverton. Take the bus back. It's just too long to do it round trip.

If you know you are not going to do the train, give yourself time to visit Silverton on your way through.

Durango is about an hour east of the entrance station to Mesa Verde. It's a good base for a MV visit. The Far View Lodge in the park itself would be a good option, assuming you can get a reservation and you aren't big on night life. If you ARE big on night life, come back to Durango for the evening, or consider staying in Mancos, just east of the park entrance. Mancos is a pretty classic old west town. Cortez is close to the park, but isn't a very nice town.

It wouldn't be too long of a trip to drive from Vail to Ouray in one day? It's hard to tell from a map what the roads would be like... twisting and curving to slow us down thru the mountains, plus we want to stop and enjoy the scenery.

Cortez isn't bad! That's where we stayed while visiting Mesa Verde. It took us only 20-30 minutes to drive to the entrance to the park. We stayed at the Holiday Inn Express in Cortez and it must be brand new because it was a very very nice hotel.
They also have a brew pub downtown with excellent food, so you know it can't be all bad. (Main Street Brewery, Main Street in Cortez)

Just be sure it is daylight when you are driving from Ouray to Durango.

Not only is it the most scenic highway in that part of the country but can be dangerous too.

It's a beautiful trip from Vail to Ouray. I lived in CO for years, then went back for a car trip and circled the state. We left Vail, heading West on I70, looked over Glenwood Springs. We then went South on Hwy 82 thru Carbondale and stayed in Redstone at a historic mountain lodge, the Redstone Inn: http://www.redstoneinn.com/. It is a romantic old place you'll love. (Travel time: about 2-3 hours).Hopefully you'll have enough time to take a side trip to Marble, a defunct marble mining town--lots of huge white chunks and slabs of marble lying around--good for photos.
Next day you can stay on Hwy 133 south to Delta, then to Montrose and finally to Ouray via Hwy 550. Delta and Montrose are out in the prairie but nearing Ouray you'll return to the mountains. We stayed in the Wiesbaden Inn & Spa, http://www.wiesbadenhotsprings.com/
It has this amazing underground Vapor Cave with hot mineral water, mineral pool (forget about the public hot pool)and you can walk to downtown Ouray where we had the best Mexican food since Sante Fe at some old hotel (cannot remember the name). The next day heading to Durango you will experience the most outrageously beautiful and exciting mountain pass in Co.--Ouray Pass. An easy drive to the Far View Lodge (right in Mesa Verde Park) mentioned in a previous post. Have a martini on your individual small deck overlooking a truely far view (clear days you can see Monument Valley) and do Mesa Verde the next day early before the crowds. Make Reservations for Far View NOW! Nothin' much in Salida. Have a wonderful trip!

Far View Lodge http://www.visitmesaverde.com/accommodations.htm
They have an 800 #

As indicated in other replies you can do Vail to Durango in One day. Whatever route you take consider a stop for a few hour at the Black Canyons of the Gunnison National Park. It is about 10 miles east of Montrose. You could spend the first night in Ouray. Since you intend visiting Mesa Verde you might consider staying in Cortez as opposed to Durango. Ouray to Durango will take 3 hours or so.

By the way, there is no big reason to stay the night in Salida. Cute town with Hot Springs, but better to stay in Ouray or use that time at Black Canyon or at Glenwood Hot SPrings, or Aspen. From Vail, I suggest going on to Grand Junction on I70, then, south to Montrose, Ouray and Durango, not back to Salida. However, if you choose to go west on Highway 50, there is a little known site between Curecanti Reservoir and Black Canyon at Pine Creek. There is a forest service boat trip deep in the canyon. You have to buy tickets at the Elk Creek Visitor center, and hike an easy mile (except for the steps) to the boat ramp. Also, the north side of the Curecanti Recreation has some stunning views especially at overlooks. However, it does take some extensive time to visit these spots.Montrose also has a relatively new Holiday Inn Express, but Ouray is a much nicer overnight spot. If you are driving through on weekends, you probably need reservations at hotels or in Durango, you need them any time during the summer.