For those playing for the first time (just in case)

Basically, you want to push through the story to unlock content first, and as many people have said, you can progress smoothly by focusing your growth resources solely on Florence. I personally progressed with Cordy until a certain point, but got stuck a few times. Once I switched to Florence, I was able to breeze through the story. (Resetting costs diamonds) It's like placing Merlin on the edge and Florence next to her. For runes, I think it's best to aim for 3 sets of 9 Penetration, then focus a bit on Speed runes, and then aim for 10 Penetration. Apparently, the final goal is 14, 14, 13.