Hundreds of ways, many bypassing the major cities, details depend on starting and destination, just which cities you can tolerate, which ones you would most like to avoid.
Realistically, the easiest and safest way is by Interstate, and it goes through Atlanta, Nashville, St Louis, and Omaha, only the first two of which tend to be real bottlenecks if you hit them at the wrong time of day. St Louis and KC have real good bypasses both ways around, with traffic light enough that some of it will be running 15-20 MPH over the speed limit (which is what bothers me about those two).
You can avoid Atlanta by using I-10 to get more to the west before going north. I like to go US-49 through Mississippi from Biloxi, (or US-98 from Mobile) through Jackson to connect with US-65/I-530 into Little Rock, I-40 to Fort Smith, where you would take I-540/US-71 to Kansas City to join I-29 going north (I don't, I'm still going west at that point). You could go on to Oklahoma City and I-35 to Wichita, or take the Muskogee Turnpike to Tulsa, then US-412 (another toll road) to I-35, but either way, once past Wichita you start running out of good routes up to the Nebraska and the Dakotas.
If I had to choose something two-lane going north from south central Kansas, it would probably be US-81 out of Wichita, up to I-80 (US-30 if you really must) then north again on US-385 out of Sidney, going into Rapid City.
A note on the two-lane highways. They can be so-so in Mississippi, Arkansas and Missouri, sometimes pretty bad in Louisiana and Oklahoma, fairly good in Kansas.
Speed limits for these on the plains tend to be 65 or higher, and local drivers like to run about 5-10 over, a lot of the big trucks at 70 or slightly more, especially grain haulers and dump trucks hauling building materials (the way they get paid is an incentive to complete more trips per day). If you will be going 50-60 MPH on this class of road in the middle of the country, you will be holding up traffic a lot more than on the Interstates, where at least the faster drivers have a passing lane.
FWIW, I do almost all of my regional travel on state highways and US-numbered highways (there no Interstate highways going where I am going), and on long trips I now make it a 50-50 mix most of the time. Getting off the superhighways adds, on the average, an extra half day of driving time for each day of the trip. Where I use the superhighways in particular is to get through large cities and to go around small cities.
Where Interstates replaced a numbered highway, and the old road still exists, the old one goes through the city, no bypass. The highway has become "main street" and there may be traffic signals every 1/4 mile, and you wait at all of them because protected left turns have greatly increased wait times. When you get to town center, speed limits often drop to as low as 20 mph, for protection of people using crosswalks and backing out of street parking.
A city of 30,000 people might take as much as 20 minutes to crawl through. A town of two thousand might slow you down to 30 MPH for 5 to 10 miles, 20 mph or less for a half mile to a mile. In much of the country, spacing of these towns is horse and buggy round trip for market days, thus every 10-20 miles unless they've become ghost towns.
The other thing I've noticed traveling this way is that some places have local traffic customs, drivers will do things you do not expect (particularly pull out or back out in front of you) because even though through traffic has right of way, local custom is to courteously yield to someone leaving a driveway or backing out into the street. But of course, you also find these variations on the superhighways, particularly how people use the on ramps, how they merge, at what speed, and who they expect to yield.
