Keep companions alive in battle. If companions die, they won’t revive until after combat ends, meaning you lose out on the support or damage they provide. When your goal is to get through levels as quickly as possible, you must avoid anything that causes delays.
Select companions that complement your hero. While you’re leveling up, take a healer and a tank. That changes when you start speed runs; your companions should change to those that help you kill enemies the fastest.
If you like a certain companion from the store, you can purchase multiple copies, but only after you have unlocked everything else you need with gems. Duplicate companions are a luxury!