The easiest way to get between Disneyland and San Diego is the way the locals do: get in a car and drive. If you need to rent a vehicle to make the trip, compare prices on car rentals at Kayak.com.
The route is simple: I-5 runs between the two cities - but driving isn't the only way. If you can't (or don't want to) drive, you have other options.
San Diego - Disneyland by Shuttle
A once-daily shuttle runs between San Diego and Anaheim, not suitable for a day trip, but fine if you're going for a day or two. Reserve your shuttle online.
San Diego - Disneyland by Train
The closest Amtrak stop to Disneyland is about two miles away. The Anaheim station at 2150 E Katella Avenue is served by the Pacific Surfliner route which will take you to Old Town or downtown San Diego. Get fares and schedules at the Amtrak website.
If you're arriving at San Diego Airport and going straight to Disneyland to start your vacation, you can take the San Diego MTS Route 992 bus to Amtrak's Santa Fe Depot downtown.