Depending upon what time you're leaving, the fastest route can be I5 to 101 or I5 to 405 to 101. (Checking some traffic apps will tell you whether to go 405 or stay on 5.).
Never much fun going thru LA. We've hit a few times leaving San Diego around 8:30-9:00AM, and that seems to get us into LA area for the lunch time traffic, but sure beats To/From work rush hour traffic hours. Usually once you get up to Calabasas area, the worst is behind you.
We've done the I15 to 210 to I5 to 126 to 101 a few times too. But the San Bernardino and Pasadena traffic can frankly be as bad as LA now a days.
And while it seems crazy, one time we went I15 to I215 to I15 to 395 - and the took 58W all the way over and thru Bakersfield and came in just North of SLO at Santa Margarita and then worked our way back that little bit down South on 101. (Was a different sort of drive, and probably and an hour or so due to longer distance. But traffic for sure was easier once we again got out of San Bernardino area...).
Look at the time our leaving, and where your heading out of San Diego region from - and flip a coin
Best to you,