Act 6
.. I recommend following this skill tree path which was explicitly designed to make the gaming experience as pleasant as possible for new players. That being said, it focuses more on survivability and comfort than damage since these are way more important at the beginning, but the guide will elaborate on options to adjust the skill tree in order to be more damage centric for the endgame later.
For killing Kitava in Act 5, you lose 30% Fire Resistance, 30% Cold Resistance and 30% Lightning Resistance. So by default, enemies now deal increased elemental damage. So focussing on getting additional elemental resistances on your items becomes even more important now.
Once you enter the Lioneye’s Watch in Act 6, head straight to The Twilight Strand (on the left) and clear it to complete the quest ‚Fallen from Grace‚. The quest reward isn’t that big of a deal, but by completing it you will unlock the store of Lilly Roth which can be helpful later.
Pantheons are strong permanent passive effects your character gets by defeating specific bosses. You can have a major and a minor Pantheon. Here, you can choose your major Pantheon ‘Soul of the Brine King‘ after killing the final boss of Act 6 by talking to Sin who provides you the following buff: “You cannot be Stunned if you’ve been Stunned or Blocked a Stunning Hit in the past 2 seconds”. This Pantheon is also your major endgame Pantheon which means you won’t change it anymore.
For now, this is optional. You can do this later as well. Trials of Ascendancy are mazes within specific areas of the campaign – in this case, The Prison.