St. Petersburg was a planned city from day one, and therefore makes sense to most visitors right away. The center of town is relatively compact, and the increasing use of English on street signs and billboards breaks up the puzzling array of Russian lettering and helps visitors get their bearings. But globalization has encroached only so far, and even though the city was Peter the Great's window to the Western world, there's no mistaking St. Petersburg's Russianness.
St. Petersburg is a coherent and carefully planned city, and the value of its individual buildings is best appreciated when you take a step back and view the ensemble to which the buildings contribute. Sculpted parks and curving canals are part of the plan, and well worth a detour -- though be sure to have a map in English and Russian, because off the main roads, street signs are usually in the Cyrillic alphabet only.
The city is Russia's principal port, and its geography and history make it immediately distinguishable from Moscow. St. Petersburg did not grow gradually from provincial backwater to major metropolis like its southern rival, this city was built up from the bogs, fast and furious, to be an imperial capital, and it served as such for 2 centuries. St. Petersburg is better at celebrating the past than at choosing a direction for the future, which means that museums, palaces, and ballet and opera houses are where its strengths lie; daring modern art and architecture are not. The Hermitage is a crucial stop but far from the only museum you should visit on this trip.
St. Petersburg's relative youth and the secular ideas of its founder, Peter the Great, mean that cathedrals play a less crucial and less religious role here than in 850-year-old Moscow. Still, your visit should include a church or two; the ones listed are architecturally or historically notable. Some cathedrals remain museums as they were in Soviet days, but many are again functioning churches and hold services throughout the day.