Loop one: the long one, with the Cuyamaca Peak climb
The first and longest loop covers the western side of the park and has the biggest sustained climbing of the day, working up toward the Cuyamaca Peak area near 6,500 feet. This is where the most vert sits, so this is also where over-eager runners do the most damage to themselves. The grades are mostly steady and runnable, not technical scrambling, and that is the problem. It is way too easy to push the climbs too hard while your legs still feel good.
So treat loop one as the loop where you bank patience, not time. Hike the steeper pitches on purpose, keep your effort capped, and come back to the start with your legs still under you. The people who blow up at Cuyamaca almost always do it by racing this first loop.