The Blue Ridge is great. Not as many turns and twists but some great scenery and little towns is US Rte 6; especially the eastern third.
That unfortunately is going to be true of most of these roads when they’re “in season.” The Big Sur part of Highway 1 is notorious for turning into a parking lot during certain times of year, for example.
You must have done this a long time ago. There used to be a very rudimentary customs station north of Polebridge, but after 9/11 they closed it, dug a tank trap across the road, and put up signs detailing the dire consequences of crossing into Canada. If anything this has only added to Polebridge’s bizarre isolated charm since before I think you could at least make a loop of it and come back through Waterton, but now it really is just a 50 mile gravel road to nowhere. I don’t think there’s any creek crossings or glacier views, although admittedly I haven’t done the 20 miles between Polebridge and the border in a long time. The North Fork Road (which is what it’s technically called BTW) is definitely a nice dirt road through the mountains, but Montana’s got plenty of those. It’s not even the most scenic road in Glacier Park, although that one definitely has the “turns into a parking lot” problem some parts of the year.
I’m going to nominate the Hana Highwayon the island of Maui, Hawaii. Absolutely spectacular!
I came here to mention Going-to-the-Sun-Road, too.
Utah 12 and Utah 128 have already been mentioned. I will also add Utah 24 between Torrey and Hanksville, and Utah 95 between Hanksville and Blanding.
US550 Between Durango and Ouray (in Colorado) is pretty nifty, with three mountain passes and a bazillion avalanche zones.
Cherohala Skyway in Tennessee/North Carolina is a nice scenic/twisty drive. Lots of overlooks and picnic areas. In Tellico Plains on the west end of it, look for a tasty sandwich shop/bakery cleverly named “Tellico Grains;” a good lunch stop.
I think this road made both lists!
Interstate 15 in Southern Utah in several places, such as where it goes by Kolob Canyon in Zion National Park
Kancamagus Highway in New Hampshire (Route 112)
http://www.kancamagushighway.com/
White Mountain Highway (I-93 north of Lincoln, NH), which goes past Cannon Mountain and the Former Old Man of the Moujntains, Echo Lake, Houston Rock, the Flume, and the Whirlpool.
http://www.visitnh.gov/what-to-do/scenic-drives/white-mountains.aspx
In Ontario, the north shore of Lake Superior (Highway 17 from Sault Ste. Marie to Thunder bay, then Highway 61 to the Minnesota border). The best sections are from the southernmost addition to Lake Superior Provincial Park up into the original park, and from Marathon to Terrace Bay.
Sepulveda Pass along the I-405 in L.A. is probably eligible for both lists.
Sonora, Ebbetts and Monitor Passes (all a little south of Tahoe in the Sierras) are insanely good motorcycle roads.
I was lucky when I went to Glacier. Wasn’t too crowded, and did the road 3 times (motorcycle) one day, and a couple more over the next couple days. Not to mention the dual-sport terror I did on the western edge and a visit to the previously mentioned Polebridge.
Good times!
Yes, this one. Plan to make many stops. Plan to swear you can’t possibly be seeing the colors you are seeing. cf: Peyto Lake.
The drive from Skagway, AK to White Horse, Yukon Territories is also fantastic.
I did this one last year. Yes, there are some tricky spots, but it’s not all like that. The scenery is fantastic basically the whole way, and many of the stop points … Kodachrome Basin, Mossy Cave, Escalante Petrified Forest, Calf Creek … are well worthwhile. Of course the anchor points, Bryce and (nitpick) Capitol Reef are both must-sees.
The Adirondack Northway between Lake George and Montreal is the most scenic road in the US. Look Magazine said so, so it’s definitive. 
The Franconia Notch Bike Trail runs along some of that route, and it’s fantastic.
A couple more in California are State Routes 25 and 49, especially in the spring.
I’ll add another vote for UT 12. If you have time, The Burr Trail out of Boulder is a really great half-day side trip.
I live in Norther California and there is no shortage of nice drives for both day trips and extended (a week or more) trips that are wonderful. Some of my favorite drives are:
Highway 1 from SF to Leggit, then 101 to Crescent City. Definitely more than a day trip.
Aside from SF and the Golden gate you pass through Muir state park, Point Reyes, and Bodega Bay. Farther along there is Mendocino and Fort Bragg near where you cut inland into the Redwoods and turn onto 101 to end up in Crescent City near the Oregon border.
Highway 49 between Nevada City and Sonora. Lots of medium to small gold rush towns, most with period ‘old town’ sections with plenty of quirky shops and restaurants and great scenery between towns.
Highway 16/20 from Woodland (West of Sacramento) to Fort Bragg. (probably best to make this one an overnight). Travel up the Capay Valley, around Clear Lake (which is nice but kind of dumpy in a trailer trashy kind of way) and on to Willits then Fort Bragg. You can also stop in Willits and ride the Skunk Train between the two towns, but the round trip is a day in itself)
Yeah, I’ve ridden it. Drove my car up to The Flume, parked, and rode my bike up to Cannon Mountain and back. I tried to interest Pepper Mill into doing the Cannon-to Flume ride (which is mostly downhill), but found no interest there.
I’ve done the drive on I-90 from Spokane to Missoula and back a few times. Awesome scenery, and great fun to drive. On a quiet Sunday afternoon in the summer/fall, at least.
This ties in with my candidate, US 93 north past the west side of Flathead Lake and into Kalispell. Same comments apply, and at Kalispell one can take US 2 into Glacier Park.
(West of Spokane to the top of the Columbia gorge belongs in the other thread.)
Throughout Central Texas when the bluebonnets are in season.
I don’t know if this is one of the best in the country, but I was really shocked at how pleasant and pretty the Palisades Parkway was between about Ft. Lee and Highland Falls. I was totally expecting grim urban landscapes and general ugliness like on the NJ Turnpike around Newark/Teaneck.
The Adirondack Northway (I-87) from Lake George, NY on North. Take the drive in the middle of October, and the colors will amaze you.