I used Neodesha, KS as Smallville and Manhattan as Metropolis several times. Mainly for On The Other Hand, I researched the drive fairly extensively and GOOD 2-3 days is reasonable. When Clark and Lana leave for college, they stopped in St. Louis [about 5 hours], somewhere else [about 12 hours] then into Metropolis [another 6-7 hours, iirc], but when Clark, Lois and Lana drove back, they did it in two days, stopping in Indiana overnight.
I think three easy days or two longer days would be pretty realistic.
