Both cities deserve more than a quick stop, and the right choice depends less on a checklist than on how you want the city to feel between attractions.
Philadelphia: choose density and history
Philadelphia is easier for a largely car-light weekend built around central museums, historic streets, markets and distinct dining neighborhoods. A central base reduces friction and leaves countryside extensions optional.
Pittsburgh: choose neighborhoods and views
Pittsburgh's rivers, slopes and bridges shape every day. Choose the neighborhood around the evenings you want, then confirm the route to museums, sports or universities rather than judging by straight-line distance.
Do not force both into one weekend
The cross-state journey is part of the trip, not a short transfer. Combine the cities only when you have enough time to give each a real stay and are comfortable using the rail day or drive as a deliberate transition.