The most convenient place to rent a car is at Denver International Airport. You can save money if you rent from the other offices of major car companies, but you'll have to take a shuttle or taxi to the city locations.
The hardest part about driving in the High Rockies is keeping your eyes on the road, what with canyons, mountain ridges, and animals to distract your attention. Some of the most scenic routes aren't necessarily the most direct, like the spectacular Loveland Pass.
Although it is often severely overcrowded on weekends and holidays, I–70 is still the quickest and most direct route from Denver to the High Rockies. It slices through the state, separating it into northern and southern halves. Idaho Springs is along I–70. Winter Park is north of I–70, on U.S. 40 and over Berthoud Pass, which has gorgeous views but also has several hairpin turns. U.S. 285 is the southwest route to Buena Vista, Salida, and the High Rockies. Any mountain road or highway can be treacherous when a winter storm blows in. Drive defensively, especially downhill to Denver and Dillon where runaway truck ramps see a fair bit of use.
Gasoline is readily available along I–70 and U.S. 285, but not so in more-remote areas like Mount Evans and Guanella Pass. Blinding snowstorms can appear out of nowhere on the high passes at any time of the year. In the fall, winter, and early spring, it's a good idea to bring chains and a shovel along. Road reports and signage on the highways will indicate whether chains or four-wheel-drive vehicles are required. Keep your eyes peeled for wildlife, especially along the stretch of I–70 from Idaho Springs to the Eisenhower Tunnel. Bighorn sheep, elk, and deer frequently graze along the north side of the highway.