Viewed from above, Houston resembles a dartboard: a series of concentric rings (highways) spreading out from the bull's eye, downtown. Since the city spreads—OK, sprawls—far and wide, encompassing an area of more than 600 square mi, your best game plan is to rent a car, get a map, and prepare for some exciting freeway driving.
The main thing to remember is that most locations can be characterized as being "In the Loop" or "Outside the Loop," the Loop being I-610, the highway that encircles the inner part of the city. (Not to be confused with "the Beltway," a larger loop highway that rings Houston near George Bush Intercontinental Airport.) Radiating out from the city's center are I-10, heading east to Louisiana and west to San Antonio; U.S. 59, heading northeast to Longview or southwest to Victoria; and I-45, heading southeast to Galveston or north to Dallas.