Presque Isle: it is the opposite end of the Commonwealth from Philly, but Lake Erie is more of a fresh water inland sea than it is a "lake" and it is well worth a visit. I'm glad that PA DCNR has the peninsula in the state park system because I could EASILY see the NPS trying to make it a national park. (While up there, also be sure to check out Erie Bluffs State Park.)

Fallingwater: even though it was built for ridiculously rich people, has some serious structural problems, and is pretty impractical Frank Lloyd Wright's design is iconic and beautiful.

While in the area: go whitewater rafting on the Youghiogheny River and/or pedal along the Great Allegheny Passage.

Go to Point State Park in Pittsburgh and kayak on all three rivers. While in Pittsburgh, check out Phipps Conservatory.

The Abandoned sections of the PA Turnpike. You can find them by going to the Breezewood exit and taking US Rt 30 east.

Go to any of the Audubon Society viewing sites during the spring or fall migrations.

Tour the Gettysburg battlefield.

The Appalachian Trail Museum in Pine Grove Furnace State Park

See Penn State's Beaver Stadium, and hike the mountain that is the origin for the name of their mascot: Mount Nittany. Also affiliated with Penn State: the Pasto Agricultural Museum (shows the history of agriculture before the internal combustion engine) and Shaver's Creek Environmental Education Center (which has reptiles and birds, including a bald eagle). Also don't pass up checking out the Scotia ghost town while in the area

Hyner View State Park (especially during a fall weekend because you might see handgliders with beautiful fall foliage)

The Quehanna Wild Area which is where testing and research to create nuclear powered airplanes was performed.

The scenic overlook portion of Shikellamy State Park.

Bethlehem, PA around Christmas time.

The Susquehanna River Petroglyphs

The Pennsylvania Farm Show

Centralia, PA

Wellsboro during late may-early June (that's when the Mountain Laurel blooms)

The Boulder field at Hickory Run State Park

The tiny bits of Old Growth Forest like the Snyders-Middleswarth Natural Area, Hearts Content Recreation Site (in the Allegheny National Forest), Cooke Forest, and others.