It depends on roster. Obviously Act 5 yields the greatest rewards, but the question of whether or not it's possible is the case. What are you trying to accomplish/do you have any goals or anything like that?
Well then the side event is your answer, Buy the chronometer and get that nick awakened. After you awaken him, I would suggest going for Act 5 exploration since Nick is good on anything that bleeds. Then, if you need revives n stuff you can grind arena. In my opinion Act 4 is only worth exploring for those mastery points so that wouldn't be a priority for me.
Comments