I find that in the US generally, and especially in rural states were towns of 10000+ are considered 'big', the listed destination points on highways are generally too provincial and small, especially on federal highways where facilitating long-distance travel is the entire point.
On I-80 for example I would sign Lincoln and Omaha all the way from Cheyenne Wyoming, with North Platte, Kearney, and Grand Island as the secondary points. (Go ahead and use for slots until GI is passed) While from the east end Denver should be signed all 540 miles from Omaha, (Lincoln, GI, Kearney, NP, and Cheyenne for secondaries), with Salt Lake City taking over as the ultimate point past the I-76 split.
I could give some other suggestions; Kansas City should be listed on southeast NE 2 all the way from Pioneers Park; that's where the majority of people using that road are going. Topeka KS, should be listed on US 75 south from downtown Omaha, Sioux City on US 77 north of Lincoln. In fact I would even go so far as to sign Chicago on I-80 from Lincoln eastward, with a couple of auxiliary signs showing the way to Minneapolis. This is so not the most boring and aspergery I could write about, honest. Put me in charge of the signs and I'll blow your mind.