NOTE: I took byways for most of these destinations, but most are accesible by highways and exits. Though to get true Americana, the blacktop monsters aren't the best way.
CHICAGO, IL to HUNTINGTON, IN
Route: Take U.S. 41 (Lake Shore Drive) South. It will turn directly into South Shore Drive and then turn left onto 87th Street and then right onto Indianapolis Boulevard once it gets to Indiana (the whole thing is clearly maked by U.S. 41 South signs the whole route). Take U.S. 41 south to U.S. 30 and make a left to head east. Stay on U.S. 30 east for about 110 miles. Turn right onto Indiana 9 and stay on this for about 20 miles. Bear right on Tipton Street and follow this into town. Turn right on Warren Street. 166 miles and approximately 4 hours, 5 minutes.
Alternate Route: Take U.S. 41 (Lake Shore Drive) South to the Chicago Skyway (I-90). Exit #31 is for Chesterton/Valparaiso. Turn right on Indiana 49 South toward Valparaiso. Take ramp onto U.S. 30 East (toward Plymouth) and stay on it for about 85 miles. Turn right onto Indiana 9 and stay on this for about 20 miles. Bear right on Tipton Street and follow this into town. Turn right on Warren Street. 166 miles and approximately 3 hours, 35 minutes.
Picking up my rental car at the Alamo over the Clark and Lake blue line stop (and under the loop stops), I set down Lake Street to Michigan Avenue to Congress Street to Lake Shore Drive. Chicago's my hometown so I could recommend about a dozen scenic routes to get from downtown out of the city (and a couple really dangerous ones like South State Street).
Still in all of my times leaving the city, I couldn't remember a time that Lake Shore Drive looked more beautiful.
The route that I took is not highly recommended because it goes through some absolutely shady sections of Chicago but I do recommed taking Lake Shore Drive to where it merges with the Skyway over one of the more traditional routes like the Kennedy (I-90/I-94). Lake Shore Drive loops around the beaches and parks of Lake Michigan in a seemingly neverending series of vistas of the lake.
South Shore Drive does the same thing through Hyde Park and Bronzeville (basically Chicago's Harlem but without the urban decay). However, if you take this route to South Shore Drive, there's no escape and you're going to be stuck either hugging the lake until Indiana (and if you're scared of the city hugging the steering wheel as well) or going through Chicago's absolute worst neighborhoods to get back to the expressway.
If you stick it out, Indianapolis Boulevard is worth every iota of worry you might have had.
The Skyway is much quicker but it passes above and too far north to see a truly great hidden secret of Chicagoland that I didn't know about - the cities of Highland and Munster, IN.
These towns are so close to Chicago that people commute in from them but two things caught my eye very quickly. The first is that the first farm I saw of the trip was off of the highway in Highland the second was that Highland has a spectacular Main Street that Indianapolis Boulevard turns into for a brief stretch.
Beyond that, this route is not very exciting but there's no way to avoid U.S. 30 (and, trust me, Yahoo and Google Maps both tried to take me back to the expressways no matter how hard I fought it). Unlike many sections of U.S. 30 (the Lincoln Highway) there is not much going on for its Indiana stretch. It's basically a big patch of sububan sprawl across the entire northern Indiana region.
This route does pass below Valpariso which is supposed to be very nice and might prove an interesting place to stop - but I didn't. Warsaw, IN seems like it could be an interesting place due to its name but it's not.
Huntington, on the other hand, is a Norman Rockwell painting with modern characters.