JetBlue offers flights from John Wayne Airport to Las Vegas for around 40 bucks each way. I have flown to Vegas for the night several times on JetBlue, and the price can't be beat.
With the price of gas at $3.35 a gallon for the lowest grade self serve in Orange County now (had to fill up this morning), and up to $3.75 for higher octane gas, it's a wonder why anyone still drives. The flight from John Wayne to Vegas takes about 40 minutes, you get a cocktail and watch some TV on the seatback, the JetBlue stewardesses are actually nice and charming unlike most other airlines now, and you're walking in to your hotel room 90 minutes after you left Orange County.
The whole thing works in reverse for those coming from Vegas to get to Disneyland. John Wayne Airport is about a 20 minute drive to the Disneyland Hotel. Rent a car from Enterprise for 30 bucks, or just take a taxi for 20 bucks, and your on Space Mountain before the people driving from Vegas across the desert have even hit Barstow.