CO 65 goes over the top of Grand Mesa. Very scenic, but can be windy and narrow and bad weather while the valleys below are sunny. It's WAY out of your way both distance and time wise and if you're pulling a rig it will be a PITA because you're going to climb and then come off a big mesa - we're talking an approximate 5,000 foot elevation change. Going down US 50 is a piece of cake, pretty much flat and 4 lane, will take about 45 minutes to get to Delta from Grand Junction. Plan several hours over the mesa. One of those cases where what looks like a shortcut is much much further. But if you like the scenic route, it's nice, but you'll be seeing snowbanks this time of year.