We've done (2) 2 week driving trips. Both to the same part of the country (Missouri, Tennessee, North Carolina, back to Iowa). Before we leave the house we know exactly where we are going, when we will get there, where we will stay and always allow plenty of time to wander at each stop. Some places get more "wander time" than others, based on what's there. Some get none; just a place to sleep.
We plan everything using the Internet. Something my wife figured out: When looking for a hotel find the area on their web site that mentions what restaurants are close. Look for national chains like Applebees, Perkins, TGI Fridays, Chilis, etc. It's a good bet that the area around the hotel is a good one if they are listed. Those chains don't set up in poor areas very often. This also lets you plan ahead for eating. Again, using Google you can map the route from the hotel to the restaurant.
On the first trip we stopped in Chattanooga, TN. It was the only hotel picked for being close to someplace we wanted to see. We ended up driving 8 miles to eat, and were told to make sure our car was locked because there was a penitentiary "over the hill, there". The entire building smelled like it had just been sprayed with pesticide. Learned our lesson.
We both drive. Your wife doesn't? Ouch! She really needs to consider a less ambitious trip if you are the sole driver. The miles you're looking at are an invitation for an accident. We always plan "slop time" in our trips - the "wander time" I mentioned earlier. I'd rather see less and be safe.
Take plenty of chips for your camera. I purchased 4GB chips from newegg.com and seem to be able to fill them. I take movies with mine a lot and they eat up memory. When we went on a cruise last Feb I bought a 40GB stand-alone drive specifically made to dump pictures into. Has slots for pretty much any card and plugs into a computer so you can copy them easily using USB. That gives two backups and peace of mind.
We use Google maps to plan routes. You can click on a location en route and drag it to another spot on the Google map to see what a difference the new route will make. Pretty cool. We then take paper maps (those old fashion ones that fold up) and draw the route on them with felt tip pens. We now have a print of the maps from Google and one on the maps.
While all this planning and mapping may seem a bit anal, having this information at hand and knowing where we are going, allows us to relax and enjoy the side trips and we know for sure that we will have that wander time we like.
Mall of America: It's a mall. Granted it's big, but it's a mall! Been there three times with wife and friends (they go every year) and we get invited. I can't do it anymore. It is B O R I N G, and wears me to the bone. There isn't a thing there that I can't get here.
Chicago: Try to make time to go downtown and take an architectural river tour. Fascinating, and you aren't doing anything but sitting and relaxing while someone tells you about the buildings and the history. We've done two and really enjoyed them. Science and Industry, Shedd Aquarium, that place where they play football, um, what do they call it?
Right across from the Natural History museum. You can take tours on double decker buses, too. Someone will give you a history lesson about Chicago during the ride. Navy Pier. Pretty neat. The high-speed "scary" boat rides aren't either - skip them. Walk Michigan Ave "Miracle Mile", go over to Rush street and gawk at Ferrari's, Lamboughini's, Maseratti's and other cars most people can't afford at a dealership there. Go to Heaven on Seventh (upstairs) and have some really, really good Cajun. Red Beans and Rice to die for! We drive over for long weekends and always enjoy it. You can stay outside downtown and take the trains in and back out. Quick and a lot easier than driving. Oh, there is a very nice restaurant at Macy's, uh, Marshall Fields, uh, whatever they call it now - get a seat by the windows. Beautiful views of downtown and excellent food.
Des Moines: If you stop here and like something a little different go to Living History Farms. It's right off the Interstate by the west mix master and shows you how people lived before electricity, cars, etc. Different, but neat. There's a huge mall not too far away if you absolutely have to go to one (Jordan Creek Town Center - it's a mall). The State Capital is a beautiful building, and is not too far from the freeway.
If you do go to Minneapolis (beautiful city) you might consider driving to Milwaukee, then to Chicago. Milwaukee seems to have a different ethnic celebration on every weekend I'm there. Great food, wonderful people. If you like good wine Cedarburg is north of Milwaukee and
Wisconsin Wineries - Cedar Creek Winery, Cedarburg, Wisconsin has some excellent wines.
Heading south on the way home? Asheville, NC is a great place to stop. Lot of arts and crafts and the Biltmore is a must see. Try driving the Blue Ridge for a while. Very pretty, but wearing on the driver. Be careful and pay attention. Learn to pull off the road for faster cars and logging trucks. You'll see graveled areas and drives. As soon as you spot one, hit the turn signal and pull off. Spotted a bear and cub crossing the highway when we were there.
I-40 will take you all the way across the south part of the country. Lots of places to stop, but distances get long the further west you get. Grand Canyon as a side trip: We just got back from Vegas and took a bus tour to the South Rim. 17 hours! 3 at the canyon. We're going back for an extended stay. I want to ride a mule down and back up. We are going back to Vegas after Thanksgiving and are planning on going to the Valley of Fire. A client highly recommends it so we'll give it a look. Lake Havasau is a bit south and holds the London Bridge.
In Arkansas you will find Eureka Springs. Nice little tourist town. Excellent Botanical Gardens, and this:
Thorncrown Chapel - laying down the gauntlet with a breathtaking revelation « Quaerentia
Niagara Falls! Sorry, missed that. We stayed at the Marriott on The Falls. Wow! 23rd floor if I remember right. Beautiful place - stay on the Canadian side. Wine tours, tours over to ?? on the lake (of the lake?) can't remember for sure. One of the all-time best trips ever. I'd do it again in a minute. Not too far from the Marriott is a restaurant where you can sit on an open roof and watch the light shows and fireworks - good food too. Take the boat that goes up to the falls. Maid in the Mist I think it was. Fun! Wrap your camera in plastic, though, you'll get wet. Get your passport early - long wait times, and don't say anything to the guards at the crossing unless they ask. Our limo driver cautioned us to only answer what we were asked and do not offer any unsolicited information.
I guarantee you I've missed a lot of places that others can mention. Take your time, enjoy the trip. It might be the only chance you have to take one like it. Don't rush.