Ocotillo Wells Directions and Map

Map above is roughly to scale.
 
From San Diego
Exit I-15 at Scripps Poway Parkway heading east
Turn left on hwy 67 heading north
Proceed through Ramona on hwy 78 heading east
Turn left on hwy 79 at Santa Ysabel heading north
Turn right on S-2 at Lake Henshaw heading south-east
Turn left on 78 heading east.

An alternate route is to take 78 through Julian rather going around via 79 and S-2. At times this can be a shorter route but the road through Julian involves steep inclines and numerous of turns. Not really worth the time saved unless you're looking for a scenic drive.
 
From El Cajon
Take hwy 67 heading north
Proceed through Ramona on hwy 78 heading east
Turn left on hwy 79 at Santa Ysabel heading north
Turn right on S-2 at Lake Henshaw heading south-east
Turn left on 78 heading east.
 
Alternate Route *
Take I-8 East
Turn left on hwy 79
Turn right on 78 in Julian heading east
 
From Escondido
Exit I-15 at E. Valley Parkway heading east
Continue Northeast and E. Valley Parkway will turn into Valley Center Rd
OR
If you are north of Escondido, exit I-15 at hwy 76 heading east

Then...

Turn left on hwy 79 at Lake Henshaw heading north
Turn right on S-2 heading south-east
Turn left on 78 heading east

NOTE: Many people take 78 through Ramona because it looks shorter on a map. It takes a lot longer due to traffic and the roads. The quickest route is Valley Center Rd to Rincon.
 
From Temecula
Take hwy 79 heading south to Lake Henshaw
Turn left on S-2 heading south-east
Turn left on 78 heading east
 
* not recommended due to curved roads, tourist traffic and potential for ice in winter months
 
There aren't a whole heck of a lot of turns outs but if you're drivings a slower vehicle, please use them when you can.