As Fodor's puts it, "the sprawling industrial city of Plzeň is hardly a tourist Mecca, but it's worth stopping for an hour or two on the way back to Prague". I agree, that Plzeň isn't worth a special trip, but if you're in the area, it is worth more than "an hour or two".
The central part of the old city has, for the most part, been well preserved. Many fine old buildings line Republic Square. (The square itself, however, is one of the ugliest I've seen. It is a vast and sterile asphalt wasteland that looks more like a parking lot.)
In the center of the square stands the Church of St. Bartholomew, an enormous Gothic edifice that boasts the tallest tower in the Czech Republic. A climb to the top rewards the effort with stunning bird's-eye views over the city. Unfortunately, the church itself was closed to visitors and only a glimpse of the vast interior was available through an iron fence just inside the entrance.
The most interesting building on the square is the Renaissance town hall, adorned with painted decorations and a fine clock. Inside the town hall is a small museum about the city and a model of the city center.
One of the joys of walking around the old part of Plzeň was discovering the ornate sculptures and paintings that decorate some of the old structures. But visitors have to remember to keep looking up! Many of these gems are well above street level and can be easily missed.
Plzeň also has a large, ornate Jewish Synagogue (said to be the third largest in the world, after Jerusalem and Budapest).
Plzeň (Pilsen in German) is the home of Pilsner style beers. The well-known Pilsner Urquell beer is brewed here and there is a fine Brewery Museum a block off the main square.