Niagara Falls NY to College Park MD

No reason to avoid Harrisburg but the traffic south of Hburg on 83, 695, and 95 will be heavier than the more western route. Perhaps best to work your way around Hburg to pick up US15 again which will lead directly to I270. As ACZL suggests it may be best for you to stay on the interstates and go to I70 from I81. A lot of choices. You definitely want to avoid rush hours between Baltimore and DC.