It's easy to find your way around St. Petersburg's center. The major sights, such as the Hermitage Museum, Palace Square, Peter and Paul Fortress, St. Isaac's Cathedral, the Admiralty, and Strelka, are all mainly along or near the Neva River, and within sight of each other. The city's main avenue, Nevesky prospekt, leads directly to the river and to the Dvortsovyi, one of its major bridges. Most streets run straight, except in places where they curve along canals or small rivers. It's helpful to keep in mind that addresses on streets that begin at the Neva go higher as they go away from the river. The smaller the number, the closer the address is to the river and to most of the major sights.
One of the city's weak points for foreign tourists is the rarity of signs in general as well as signs in English (an exception is the metro, however, where stops are identified in English). The names of the streets are written in Cyrillic, so it's well worth spending some time familiarizing yourself with its letters before you arrive. In any case, don't forget your city map. Finally, although a lot fewer people in St. Petersburg speak English than in cities in Western Europe, there are still more and more of those who do. It's always worth asking a passerby for directions (the young or middle-aged are most likely to understand).
City Center. The City Center embraces Palace Square, the Hermitage, and the northern end of Nevsky prospekt, with the Fontanka River as its southeastern border. Most of St. Petersburg's major attractions are within this area.
Admiralteisky and Vasilievsky Island. To the west of the City Center is the smaller neighborhood of the Admiralteisky, surrounding the Admiralty building. Second in number of sights, including the Chamber of Art and the Rostral Columns, is Vasilievsky Island, opposite the Admiralty and set off from the City Center by the Little and Great Neva rivers.
The Petrograd Side. North of the City Center and the Neva River is the Petrograd Side, which holds Peter and Paul Fortress and the sights of Petrograd Island.
Vladimirskaya (Lower Nevsky Prospekt). On the mainland, Vladimirskaya is an area south of the Fontanka, taking in the lower part of Nevsky prospekt and bordered by the Obvodny Canal.
Liteiny/Smolny. This region lies to the northeast of Vladimirskaya and includes the Smolny cathedral. Still farther afield, the Kirov Islands (north of the city) and the Vyborg Side (in the northeast corner of the city) have a few sights.