You won't find a better location than the Horton Grand Hotel, 311 Island Ave. (tel. 800/542-1886 or 619/544-1886). This historic Victorian beauty has called the Gaslamp Quarter home since 1886, and some otherworldly guests have reputedly been hanging around since then, too.
In San Diego's Little Italy, La Pensione Hotel, 606 W. Date St. (tel. 800/232-4683 or 619/236-8000), feels like a small European hotel and offers tidy lodgings at bargain prices. There's an abundance of great dining in the surrounding blocks, and you'll be perfectly situated to explore the rest of town by car or trolley.
Like some other recent hotel projects around town, the Hotel Occidental, 410 Elm St. (tel. 800/205-9897 or 619/232-1336), is a refurbished old beauty, circa 1923, and has a great location (near Balboa Park). Unlike those other properties, the Occidental is incredibly affordable.