I currently use about four main variations for pushing the Prowler.
I rotate these around for a given weight, generally in this order:
1) High Only
2) High Out, Low Back
3) Low Out, High Back
4) CRC Sprints
High Only, Heavy - whenever I up the sled to a new weight, I first do it high handles only. The high handles are noticeably easier, so although the loading is heavier most people will almost feel this is a vacation or a deload compared to high-low combinations. This is also a great way to get in leg work for people with spinal loading issues (back injuries, spinal surgery rehab, etc.) or as a low-technique heavy exercise. It also requires no grip work at all, so it's ideal for people who need to improve their leg strength now but don't have the grip for heavy deadlifts or single-leg lifts.
High Out, Low Back - Push the sled out with the high handles, and return with the low handles. This is the next hardest. The low handles are much more stressful than the high handles, and will get your heart rate up much faster. The high handles tire you out a little but don't take so much out of your that the low handles are so difficult.
Low Out, High Back - This is harder because the low handles really get your heart rate up and tire you out more (because of the angle). It will force you to push the high handles back while your heart rate is high and your legs are already a bit tired. It's more akin to a strip-set (do some reps, drop the weight and keep going once you can't continue) while high-low is more like warmup-work set.
CRC Sprints - CRC stands for Continuously Running Clock. Start a stopwatch and do one sprint with the Prowler down and back to the start point. Rest until you hit the one minute mark. Do it again, and repeat on every minute mark. Your rest therefore depends on how long it takes you to sprint the sled - the faster you go, the longer the rest (but the more tired you are). The goal is to continue until either a deadline (10 trips would take 10 minutes) or until you can't go on the next minute mark. This is very stressful, and I usually drop the weight significantly the first time we do it to get the client used to the approach. I also advise using a short course, because you have very little time to run it back and forth. If your first trip takes more than 30 seconds, it's probably either too heavy or too long of a course.