Centro Histórico -- This is the heart of historic Seville and contains its most imposing sights. Of these, the massive Seville Cathedral (Catedral de Sevilla) is the dominant attraction. It's the area where you'll want to spend the most time, and it's also where you'll find the finest hotels and restaurants.
Barrio Santa Cruz -- This is an area of wrought-iron cancelas (gates), courtyards with Andalusian tiled fountains, art galleries, restaurants, cafes, tabernas, flowerpots of geraniums, and winding narrow alleyways. The former ghetto of Seville's Jews, it's today named after a Christian saint and is the single-most colorful part of the city. Exploring is best done during the day (muggings sometimes occur at night). Filled with interesting sights, such as Casa Murillo and some fascinating churches, it's one of Andalusia's architectural highlights.
La Macarena -- Thought to be named for a Roman, Macarios, and the site of his former estate, this is a famous quarter of Seville that seems sadly neglected by visitors, who spend most of their time in the two quarters discussed above. It's filled with interesting attractions such as the Convento de Santa Inés (reached along Calle María Coronel). According to legend, King Pedro the Cruel was so taken with Inés's beauty that he pursued her incessantly -- until she poured boiling oil over her face to disfigure herself.
Triana & El Arenal -- These two districts were immortalized by Cervantes, Quevedo, and Lope de Vega, the fabled writers of Spain's Golden Age. They were the rough-and-tough seafaring quarters when Seville was a thriving port in the 1600s. In El Arenal, the 12-sided Torre del Oro (Gold Tower), built by the Almohads in 1220, overlooks the river on Paseo Cristóbal Colón. You can take the riverside esplanade, Marqués de Contadero, which stretches along the banks of the river from the tower. The area's Museo Provincial de Bellas Artes houses Spain's best collection of Seville's painters, notably Murillo. Across the river, Triana was once the Gypsy quarter but has now been gentrified.
Note: This information was accurate when it was published, but can change without notice. Please be sure to confirm all rates and details directly with the companies in question before planning your trip.