At higher altitudes, the engine will still run smoothly because the computer compensates for fewer air molecules entering the engine by injecting less fuel. Even back in the carburetor days, the fuel was mainly metered by the airflow passing the jets and so altitude wasn’t a big issue, although sometimes cars that lived at high altitudes would require high altitude tuning kits to meet emissions standards.
However, as the air gets thinner, the effective compression ratio of the engine goes down (since it’s squashing fewer air and fuel molecules), and you lose power. In theory, once you get high enough the engine won’t produce enough power to keep itself running and will stall, but that doesn’t happen at any driveable altitudes.
You don’t really notice altitude when you’re driving as much these days simply because cars are so much more powerful than they once were. When people were driving 36-HP VW’s and two-ton land barges with wheezy 6-cylinders, you really noticed when you started losing those horses as you climbed, but in a modern car unless you’re on a race track you’ve got quite a lot of power to spare. The power loss is also somewhat offset by lower drag when you’re actually driving.