This is my neighborhood. I live in Harrisburg.
Either one should suit fine. Route 15 to Williamsport is not bad, but certainly not interstate. You get long stretches of flat 4-lane as it follows the river. It's not interstate, so there are left-turn lanes, some stop lights, and plenty of adult stores.
As you get further north toward Allenwood, 15 cuts away from the river and you do go over one mountain. It's not steep, and not curvy. Once you reach the bottom you do go through South Williamsport with a couple traffic lights, but nothing that prevents you taking a large vehicle. It's a pretty frequent trucking route, and it is large-vehicle friendly... as evidenced by the 13'6" x 53' tractor trailer in this street view.
Once you get north of Williamsport, 15 is very interstate-ish. 4-lane, limited access, exit ramps, etc.
If you're looking for the most direct route and don't mind some 4-lane, in-town stuff, don't shy away from 15. It is perfectly RV-friendly. If you are someone who craves interstate-type driving, you can do the 81/70/99 route. I've done it many times. Don't do the turnpike (76) part. 70 will take you to Breezewood, then it will tell you to take the Turnpike one exit to Bedford to get 99. And they'll likely charge you $6 to go 15 miles. Take US30. It is totally RV-friendly. 30 takes you south of Bedford so you never really need to do much town or stoplights, and it looks a lot like the first picture I posted in this response. Then you get 99 to the south of Bedford so you never have to deal with streets. Long story short... if you go that way, replace the segment of 76 with US30 instead. Save the turnpike money and buy yourself a beer/soda in Watkins Glen when you get there. I have family in Bedford and I drive there 5 times a year. I take the turnpike to Breezewood/70 and then take 30 the rest of the way because it saves me a few dollars and only costs 3 minutes of time.
I also agree with John Welsh. The jaunt that takes you up 79 through WV is berkeleying gorgeous... and berkeleying painful. So many mountains. Up, then down, then up.... not that you aren't familiar with hills, I just don't see the need to spend the gasoline and brake pads on all that hillery (that's a real word)
Boiling it down to my recommendation. I-81 is your huckleberry up to Hagerstown. From there
- if you crave all interstate, take 70 to Breezewood, 30 (or money for 76) to Bedford, and 99 up to the strange madness of highway numbering around Williamsport. It will take a bit longer time that way, but it's all big roads.
- if you want to shave time (but have some towns and stoplights sometimes) keep on 81 to Harrisburg and take the 15 route.
My recommendation... take 15. Shorter time (by maybe half hour) and only mild inconvenience.
If you happen to choose the Harrisburg/15 option, My driveway would be about a 9-minute deviation. If you need anything, PM me.