I-5. The 5. It's the granddaddy of the freeways, and it will take you from the Mexican border up the coast, all the way to Canada if you don't pay attention. These days, it's pretty busy all hours of the day, but rush hours can try one's patience, especially at major junctions of other freeways, especially the notorious 5/805 split in Sorrento Mesa.
I-5's little brother, the 805 is the inland counterpart to the 5. Bisecting San Diego's bedroom communities, the 805 has become more and more busy in the past decade as commuters flock to more affordable housing in South Bay area. The scenic bridge across Mission Valley breaks up driving monotony, but beware its terminus up north at the notorious 5/805 split.
This schizophrenic freeway, which starts at Interstate 5 in the South Bay and heads north to the inland San Diego suburbs of Mira Mesa, Rancho Bernardo, Escondido and Riverside County, used to dribble into a surface street thoroughfare in mid-city before becoming a freeway again. Construction has finally completed the freeway project, but it still is a messy commute back to the North County. For several miles, it has a reversible High Occupancy Vehicle (HOV) carpool lane.
State Route 163
This freeway stretch, which connects I-5 downtown with I-15, is notable for its absolutely scenic stretch through Balboa Park. It almost makes it worth putting up with the traffic.
The 8 runs from Point Loma east to El Cajon and all points east. It's the main east/west freeway, traversing through commercial Mission Valley, up the grade past San Diego State University, through the suburbs of La Mesa and El Cajon and east to the San Diego County backcountry and mountains. All the major north/south freeways junction with I-8, so commutes are often a mess at those points.
State Route 94
Also known as the Martin Luther King Freeway, this is the eastern route out of downtown. Though busy, Highway 94 isn't as bad as the 8, and is often a good southern alternate route. It junctures with the north/south State 125 in La Mesa.
State Route 78
The major east/west freeway serving North County, this freeway is almost always a mess during commutes, trying to get drivers to and from their homes in the Escondido, Oceanside, Vista, and San Marcos areas. Unfortunately, there aren't many other alternatives for these commuters, so they've resigned themselves to the daily headaches.
State Route 52
One of the newer freeways, this freeway is a northern alternate to I-8, taking commuters from Clairemont in the west to Santee in the east. As more commuters discover this route, it is becoming congested as well.