The Great Plains have had two major impacts on the United States.
First, in the years before the Civil War, the Great Plains were part of the cause of disputes between the North and the South. As the US spread out over the Great Plains, conflicts arose as to whether these new territories and states would have slavery. This can be seen in such things as the Kansas-Nebraska Act and the "Bleeding Kansas" incidents that followed.
During and after the Civil War, the Great Plains became an area for expansion and for the settlement of new immigrants from Europe. The coming of the railroads opened these areas for settlement. This helped lead to the idea that any American man could go west and make a life for himself and his family. This also led to the Indian Wars.