I tried to set up a highway network in SimCity 4. I built it, but nobody's using it. They prefer roads. Maybe I have to wait a little longer.
Make sure there are off-ramps near your busiest ground-level intersections. Sims won't go way out of their way to use a highway or mass transit system, unless it takes them where they want to go. If they need further encouragement, consider toll booths on some of the more heavily trafficked ground-level throughways. Sometimes avoiding a toll is the gentle nudge your sims need to take the highway. (And if it's not, then Cha-CHING! I have whole cities that earn more in toll collection than property tax.)
If you can make it work, you'll find that in SC4, a robust, well-designed mass transit system will help your city grow. I personally tend to use a combination of a couple of highways slicing straight through the city (usually the sole links to neighboring cities), with bus and subway lines backing it up and serving outlying areas. Bottlenecks on the ground-level roads and highways tend to wind up with toll booths to generate revenue and encourage use of the bus and subway systems. All these alternatives prevent any one of them from becoming tremendously congested, making it feasible for residents and jobs to really pack into your densely zoned areas, without winding up with buildings abandoned, due to workers being unable to commute there and back in a reasonable amount of time.
[edit] Also, the Route Query tool is your friend. Find the congested intersections and bottlenecks in your town and see where the commuters in those areas are coming from and going to. This will help you better place your on/off ramps and mass transit stops. [/edit]
