Monster-Based
Monsters are an essential part of "D&D" and city campaigns are no exception. Think about the places monsters can appear from during your city campaign as a starting point; if your city features a graveyard, undead creatures, such as zombie,s could arise in the night and startle city dwellers. A city with a port could face a threat from a sea monster attacking ships or incoming pirates. Monsters, such as wererats, critters, such as giant spiders, and more terrifying creatures lurk in a city's sewers or underground tunnel system.
Location-Based
A campaign's adventures can revolve around the specific buildings found in a city. A nobleman's palace or mansion presents a large, but contained, area for players to explore; the players could investigate the secrets such a building holds. A city's temples and churches also make for intriguing adventure locations, filled with holy relics, gods and even cults. If your city has a castle, players could end up investigating its remote spots, such as its haunted cellars or perhaps a dungeon full of innocent prisoners. A more unusual setting for a city adventure is at a settlement's fighting arena, or coliseum. Here, combatants duel for gold and glory: a highly suitable set-up for warrior characters to get involved.
Types of City
The campaign you run will be heavily influenced by the kind of city in which you set your adventures. While many individuals will be happy to set a campaign in a medieval city, complete with the usual "D&D" elements, such as soldiers, noblemen and wizards, your city can be more unusual. Consider who rules the city --- perhaps a cabal of liches or coven of witches holds the power, or maybe all the city's leaders are also priests. The city's architecture can interest players, too; a city may be organic in nature with houses built among woodland or perhaps the city is partially submerged in water. The city's laws also matter; a city where magic is banned, for example, is a challenge for many players.
Plots &Quests
Plots drive the action in the campaign and can come from within a city as well as without. Crime is a factor in an urban environment; the players might go up against an organized crime syndicate, a thieves' guild, or perhaps a band of secretive assassins. Disease is also a consideration; a magically-engineered plague, for instance, could require the players to set out to discover its origins. Cities don't exist in stasis and players can face threats from outside a city's walls. For example, players might assist a city's guard in fighting off an invasion by a foreign power.