Lancaster would be the closest only on your "ideal city" recommendations. The good transportation connection to other areas criterium separates Lancaster from the others as their bus system, while inaccurate, goes pretty far in the county, as well as the Amtrak station and Greyhound buses for travel outside. Harrisburg is the only other one with an Amtrak station.

I love all the those cities for what you mentioned as each have their indidvidual charms in my world, plus craft breweries (with exception to Reading, but West Reading is walkable). Harrisburg has a great gentrified area in Mid-town as well as the State Library (whenever that reopens up again). Reading has great hiking trails nearby on Mt. Penn and Neversink mountains; as well as events at Santander arena. Lancaster has a lot of tourist/history spots/central market as well as a very good county park to camp just right outside the city. York has a decent downtown with history, Central Market, and a wonderful rail-trail. Lebanon has Snitz Creek brewery and the rail-trail that goes all the way down to (near) Etown.

All of them have something, but I believe to start out, Lancaster is your way to go and go from there.