Depends on your point in the game. Earlier on, offense is going to progress you through much faster than defense since Rift (prize fight defense doesn't matter) bases take a while to build and get effectively running with catalysts and stat builds and whatnot. Being able to comfortably clear bases and collect at least Gold 1 rewards (and also 10% prize fight rewards) is more of a priority in the beginning. Once you're at a state where you have a steady flow of resources and good defenders and catalysts at your disposal, you can focus on defense.
With that being said, Snake Bite and Class Cutter are both excellent offensive variants, so which you invest in first depends on how much you like the respective characters' playstyles. Defensively, Plot Twisted is the best out of the variants listed imo since Frost Armor is so strong, but to get the most mileage out of her you'll want RTS and at least one other water Squigly (the third can be Immoral Fiber) in a trio node. Assassins Greed and Dream Band are great as well, but I find PT to be more of a priority given you have the necessary resources to construct a FA + RTS node.
