Wife and I are driving to HOF Baseball Museum in June. Want to see if anyone has made trip in last few yrs from Houston TX area and has a preferred efficient route. MapQuest gave 3options. We know we want to come home through Erie PA, Cinn OH, Nashville,Memphis TN etc because we will be doing some day trips on return drive home. Any suggestions is appreciated. JR

I would do 2 on the way and more on the way home. My suggested route (could be reversed), I-10 into Louisiana to Baton Rouge. Take the Natchez Trace (US 61) north to Vicksburg MS. I-20 to I-55 North to Memphis.
That may be a long day but it's quite scenic. Leaving Memphis I-40 east to Nashville (lunch?). Continue east on I-40 to I-81 in eastern TN. Take I-81 N up into the beautiful Shenandoah Valley of Virginia (maybe Roanoke or Natural Bridge). I-81 will take you all the way through MD and PA to Binghamton NY where you get on I-88 just past Oneonta to the turnoff to Cooperstown (Rt. 28).
The return trip is west on the New York State Thruway through Rochester and Buffalo. You might want to stop to see Niagara Falls. If you have passports, go to see the Canadian side as well.
Continuing west from Buffalo see what you want to see in Erie PA.
The quickest way from Erie to Cincinnati is probably south on I-79 through Pittsburgh to I-70 west to Columbus OH and I-71 into Cincinnati. You could come home via Louisville and St. Louis.