Go Rt. 15, I-81 will take too long. I am originally from Niagara Falls, NY, moved to the Harrisburg area in 1986. Did the Rt. 15 run hundreds of times in all weather the 20 years I lived there. Went back this summer with the Scamp
to visit old neighbors and friends in Harrisburg and then up to Buffalo. I was very impressed with what PA has done with Rt. 15. Most of it is now 4 lanes to NY. About an hour north of Harrisburg is Selinsgrove/Shamokin Dam. You'll know it because you have to get off the 4 lane highway and are funneled thru town. Stay in the left hand lane, the semi trucks usually stay in the right and they slow traffic down. It is traffic light
after traffic light
for about 5 miles. It is the one place that has bottle necks because of the traffic lights
and trucks. But it's been that way since I travelled from 1986. Watch the route signage in Williamsport. You have to make a left turn just after crossing the bridge, then about 4 miles there is an exit to continue on 15N. When you get into NYS, it turns into I-390 to Rochester. It took me about 4.5 hrs to get from Duncannon, PA to Lancaster, NY.
Have a safe trip.