While it may be more fun to jump on the buggy and get the full story-rich tour of the city, we were too late to book slots, so we opted for the self-paced audio tour of Plzen's historic district. You can pick up a headset and audio guide + accompanying map at the Tourist Information center right on the city's main square. They told us the walk would take around 1.5 hrs, but we dawdled a bit, took the stairs to the top of St. Bartholomew's Cathedral and popped in a place or two, which extended our tour for most of the morning. Nonetheless, when we finished, we felt like we had really gotten a sense of the history of the city and seen a fair amount of what was in and around the Square.
The audio guides also have photos and videos to accompany each stop which is helpful if a) you aren't sure you're standing in front of the building you're hearing about and b) if you aren't interested or able to go inside--you might still get a glimpse.
All in all, a pretty good way to go.
Tip: I brought my own headphones which worked just fine.