Start off with “the biggest city in the biggest state in the Lower 48,” and superlatives abound in the sprawling metropolis that is Houston, Texas: “energy capital of the world,” America’s No. 1 port in international commerce, an emerging leader in alternative energy, home of the world’s largest concentration of healthcare and research institutions. And its name was the first word spoken from the moon: “Houston, Tranquility Base here. The Eagle has landed.”

Nicknamed the “Bayou City” for its 10 winding waterways, Houston has made the lists for Best Places for Business and Careers, Best Cities for College Graduates, Best Cities to Buy a Home and Best Cities of 2008. One of the last American cities to slip into recession and one of the first to emerge in January 2010, Houston is super-sized and super-ambitious.

Now expanded to 600 square miles, the original settlement measured only 6.6 acres in 1836 when two entrepreneurial brothers bought the site and named it for General Sam Houston. Initially a link to the nearby port at Galveston, Houston eventually developed its own manmade deepwater harbor. Fed by numerous railway lines, the city quickly emerged as a commercial and railroad hub for the export of cotton.

And then there was oil. The 1901 discovery at Spindletop spurred development of the petroleum industry. In addition to drilling, Houston built petrochemical refineries and manufacturing plants to supply pipes and oilfield equipment. Industry contributes to air pollution levels, but high oil and gas prices nourish the city’s economy. Six supermajor energy firms operate from here: ConocoPhillips, Marathon, Halliburton and El Paso Energy, as well as the U.S. headquarters for BP and Shell.

With the mid-20th century establishment of the Texas Medical Center, Houston became a leader in biomedical research. Almost 74,000 people work in its 49 not-for-profit institutions specializing in every aspect of healthcare: cancer, cardiology, organ transplantation, terminal illness, mental health, dentistry, wellness and prevention. More heart surgeries are performed at the Texas Medical Center than anywhere else in the world.

An additional major economic factor, the aerospace industry has grown up around NASA’s Space Center Houston, which opened in 1964. Home of Mission Control, it leads space race discoveries, training astronauts and developing space shuttles and space stations.

In the 1950s, the availability of air conditioning provided impetus for many companies to relocate to Houston, resulting in an economic boom that shifted the city’s economy toward the energy sector. Since the 1990s recession, Houston has made efforts to diversify its economy, reducing dependence on petroleum and focusing on aerospace and healthcare/biotechnology. Only New York City is home to more Fortune 500 headquarters within the city limits.

Manning all these activities is a highly literate, international population. More than 360,000 students study at the city’s more than 60 colleges, universities, medical schools and degree-granting institutions. At least 90 languages are spoken by the 2.2 million residents of the multicultural metropolis, which has the country’s highest percentage of Hispanic and Mexican Americans and a significant number of immigrants from Nigeria, China, Vietnam, India and Pakistan.

Electing Annise Parker in 2010, Houston became the largest American city led by an openly gay mayor. Politically diverse, with the balance of power swaying between wealthy Republicans and middle-class Democrats, the city is often a contested area in the conservative state’s elections.

The only major American city with no zoning restrictions, Houston’s independent spirit is expressed in patchwork neighborhoods which radiate from Downtown, the historic center which is seeing a migration back to its central core. Recently developed parks such as Discovery Green and Market Square enhance the Downtown atmosphere. Easily managed on foot, the center lies above a seven-mile Tunnel System that provides air-conditioned access to 77 businesses during the summer’s hot, humid weather.

Just steps from Downtown, a bustling Theater District presents year-round ballet, symphony, opera and theater. Several distinguished museums are located around leafy Hermann Park. To the west, colorful, artsy Montrose borders on the upscale mansions of River Oaks, the neighborhood of former President George Bush. Further west is a shoppers’ paradise centering around the indoor Galleria mall.

Automobiles dominate transportation in the oil-rich city: 71.7 percent of Houstonians drive to work on a system of freeways and expressways radiating out toward two concentric beltways. In 1978, the city voted a one-cent sales tax to convert broken-down buses into a comprehensive transit system of buses, trolleys and a 7.5-mile Metrorail with 16 stops running north-south from Downtown through the medical center to the stadium.

Diversions

Cultural life is so rich that the most difficult challenge of amusing yourself is choosing among all the myriad things to do. The city’s official website lists attractions from arts and theater to dining and special discount offers (“100 Ways to Save”). Also on the website, “What To Do Along the Rail” suggests dining and entertainment options at each stop of the Metrorail.

Resident ballet, opera, theater and symphony companies perform year ’round in the Theater District. Richly endowed by local fortunes, the Museum of Fine Arts (1001 Bissonnet St., tel 713 639 7300) pairs with the famous private Menil Collection and its renowned Rothko Chapel (1515 and 1409 Sul Ross tel 713 535 3180) showing the highest-quality exhibits. Sports fans can catch the Astros, Texans, Rockets, Dynamo and other teams in action.

The port offers free cruises of the harbor on its public tour boat leaving from Sam Houston Pavilion (7300 Clinton Drive, Gate 8, tel 713 670 2400). Activities at Space Center Houston (1601 NASA Parkway, Clear Lake, tel 281 244 2100) include interactive visits to the space station and the moon. Out near the Bush airport, artifacts from Elvis, JFK, John Wayne and Nixon are displayed in the National Museum of Funeral History (415 Bevan Springs Road, tel 281 876 3063).

Washington Avenue is the hot area for nightlife. Bordering Downtown, the street is essentially two miles of restaurants and bars. Max’s Wine Dive (4720 Washington Ave., tel 713 880 8737) has comfortable leather chairs and serves Champagne with Southern-fried chicken. Young professionals mingle, dance and devour sirloin sliders at Washington Avenue Drinkery (4115 Washington Ave., tel 713 426 3617). Through the eye-catching whiskey-barrel-shaped door of Taps House of Beer (5121 Washington Ave.) you’ll find 93 brews on tap.

Info To Go

The Houston Airport System includes two city terminals. George Bush Intercontinental (IAH), the eighth-busiest U.S. airport, lies 22 miles north of town. More convenient, seven miles south, is William P. Hobby (HOU). SupperShuttle shared rides, courtesy vans and Metro buses serve the airports. Taxis from IAH (about $50) take 30 minutes. Non-stop Metro Airport Direct buses ($30) make the 30-minute run every 30 minutes. Taxis from HOU ($30–40) take about 15 minutes. Visit www.visithoustontexas.com.

Lodging

La Colombe d’Or
The former mansion, in walking distance of the Galleria, is the five-room “world’s smallest luxury hotel.” Adjacent villas feature balconies, kitchens, Jacuzzi tubs. 3410 Montrose Blvd., tel 713 520 1770, $$$$

Hotel Granduca
A luxury boutique hotel located in the Uptown/Galleria area, Hotel Granduca boasts 123 guestrooms, including a three-bedroom suite. 1080 Uptown Park Blvd., tel 713 418 1000, $$$$

Hotel ICON
Once the home of the city’s first investment bank, the comfortable Downtown hotel exudes updated Victorian charm, steps away from Metrorail access. 220 Main St., tel 713 224 4266, $$$

Dining

Brennan’s
The popular, 43-year-old Texan Creole eatery is back in business after restoring its historic building, devastated by fire in 2008’s Hurricane Ike. 3300 Smith St., tel 713 522 9711, $$$

Ocean’s
This period home with shaded gardens offers an urban retreat serving modern Mexican cuisine. Killer cocktails and ceviche made to order daily. 819 W. Alabama, tel 713 520 7744, $$$

Reef
Inventive James Beard Award Nominee Chef Bryan Caswell prepares seafood with Gulf Coast, Mediterranean and Asian influences. 2600 Travis, tel 713 526 8282, $$$