San Isidro has some of the city’s best hotels, many of which cater to business travelers. There is a greater variety of lodgings, including low-cost and midrange options, in Miraflores and Barranco, which also have more restaurants and nightlife. These neighborhoods are quite safe, so you don't have to worry about taking a stroll (day or night), and they're quick cab rides from El Centro. The only decent hotel near the airport is in its parking lot, and is quite pricey, but it's just a 20-minute drive to the historic center (longer during rush hour).
The historic center has few decent hotels. If you decide to stay in or near the heart of the city, it's generally unsafe to go for a stroll at night outside the two main plazas and the pedestrian mall that connects them. You'll also have fewer options in terms of bars and restaurants than in other neighborhoods.