By road
Although uncommon, hitchhiking is fairly well-received, especially in more rural areas. Keep in mind that it is always illegal to hitchhike on highways closed to pedestrians, so it's better to find a rest stop or a gas station right off the highway. I-80 in particular has many good hitchhiking spots and is the recommended route for someone trying to thumb their way across the state.
By car
In addition to the Interstate highways that enter Pennsylvania and travel throughout:
The Pennsylvania Turnpike I-76 is a toll freeway that is the main east-west route between Philadelphia and Pittsburgh, with state capital Harrisburg along the way. Take note of the four tunnels through Appalachian ridges.
The Turnpike's "Northeast Extension" I-476, also toll reaches north from Philadelphia to Allentown and Scranton. Another tunnel is found along it.
U.S. Route 322 travels diagonally from the Philadelphia area to just below Erie. Many portions have been converted to freeway, but numerous small towns still lie directly on the way.
U.S. Route 22 is an alternative, more mountainous path west through Altoona and Johnstown to Pittsburgh.
U.S. Route 6 is a long, rural, scenic drive across Pennsylvania's "Northern Tier". Go west from the northern Poconos through the valley of Scranton and its suburbs, follow the Susquehanna River through the "Endless Mountains", spend three hours through state and national forest land, and end near Lake Erie.
U.S Route 30, also named the Lincoln Highway, is a section of the first coast-to-coast paved road in the United States. The highway is especially nice in the central part of Pennsylvania where it passes agricultural areas and is the main street of many small historic towns. Many of these towns have attempted to capitalize on their location on the Lincoln Highway by preserving original structures and opening them as visitors' centers.
Interstate 80 runs east and west throughout the northern area of the state.
There also exists a wide network of state highways and municipal roads that reach into the mostly forested and farmed rural areas. The more mountainous of these areas should be traversed with caution by visitors as they can be drastically winding, narrow, or steep or all three! in parts.
Speed limit signs are almost exclusively posted in miles per hour, "mph". Seatbelts use is mandatory, and a second ticket and fine will be issued to those who are pulled over for speeding, etc. if not worn. Pennsylvania has not yet enacted a ban on hand-held cell phone usage while driving, as some neighboring states have, although the cities of Philadelphia, Allentown, Bethlehem, Erie, Harrisburg, and Wilkes-Barre have enacted bans.
As conditions go, Pennsylvania has two seasons according to an old joke: winter and construction. In the rural majority of the state, large snowfalls render the most minor of roads impassable, but the major thoroughfares like Interstates are comparatively well plowed and salted. Still, car travel anywhere should be done with extreme care in the winter, especially by those unfamiliar with the visited area.
Likewise, the jest rings true in the remainder of the year. Look out for occasional paving, line painting, or road widening projects on freeways that restrict travel to a single lane. Bridge repair or any major redesign may force detours that are typically marked clearly. Speed limits in work zones are always reduced and State Police will impose double fines for breaking them. Proceed carefully around PennDOT state transportation department crews, who are easily visible in fluorescent yellow attire.
Wild animals, most notably deer, can be a problem when driving on rural Interstates and highways. Pennsylvania currently has an overpopulation of deer, so try to avoid them crossing the road.