Depending on how you count, I suppose, there are basically four main east-west highways crossing Montana: US 2, US 12, Montana 200, and the Interstate. My least favorite of those, by far, is the freeway ... the road is a scar on the land, and when you drive on an Interstate you miss the little towns and all the other cool sights that make a roadtrip interesting and fun. All the two-lane roads are great journeys, though US 2 is probably a little less rewarding for me than the others.
For a drive that shows the vastness and emptiness and wide-ranging beauty of Montana, Highway 200 is hard to beat. I'm a particular fan, though, of US 12, which has a great mix of mountains and prairies and Badlands country, along with some of my favorite small towns. The road follows the Musselshell River for 140 miles or so, a valley that's unremarked but surprisingly lovely.
Here's a shot I took last month of US 12, heading east down the Musselshell: