Medic as primary (You'll want to be able to regenerate relics during boss fights, especially the final bosses; I know it's tempting to use Challenger for his cheat death, but you'll be very salty if you run out of relics)
Challenger with Juggernaut (Rampage is good for mobs, but Juggernaut is king for boss fights)
Entire Leto Mark 2 armor set, except the gloves; If you've unlocked Archon, the Labyrinth gloves are slightly lighter but have a higher armor value.
Resonating heart for mobs, Crystal Heart for bosses. (I know Crystal Heart makes you feel stuck in mud, but the massive damage reduction will save your bacon)
You want the Mythic Health, Mythic Damage Reduction, and Mythic Healing Effectiveness fragments. Make sure to upgrade when you're playing higher difficulties. Mythic is a huge leap in quality.
Amulet; Twisted Idol (Extra armor effectiveness AND brings your weight down to 65, no flopping babyyy)
Blessed Ring
Ring of the Robust
Rerouting Cable
Hardcore Metal Band
Bark Extract for your concoction
Traits:
Triage 10
Strong Back 10
Regrowth 10
Fortify 10
Vigot 10
Spirit 10
Barkskin 10
Fitness 10
Expertise 5
Glutton 5
That basic Damage Reduction on that build is 72.7% before any buffs kick in. You'll basically smash the 80% cap any time you're actually fighting. With all the buffs, I hit 81.4% damage reduction at the firing range.
Weapons are really up to you. Damage isn't going to be your strong suit.
I mostly used the Blackmaw with Twisting Wounds mutator and Hot Shot mod
Hero's Sword
Enigma
But, I used a lot of different setups on the run. I didn't stick to anything religiously. The Crescent Moon is probably the best weapon in the game, but I can't hit the perfect timing consistently enough.
Some of the rings bounced around a bit as well. It's a lot of trial and error; What I listed is what I used for Root Earth. I know I said Crystal Heart for bosses, but I did run Annihilation with Resonating Heart, because it has a longer active time, so I didn't have to pause to use the relic so frequently. To counter Crystal Heart a little, you can use Nimue's Ribbon amulet to gain some movement speed after using Crystal Heart, but you'll want to swap Ring of the Robust for Ring of Omens so you can still roll. That setup looks like:
Nimue's Ribbon
Blessed Ring
Ring of Omens
Dense Silicon Ring (Free healing/mod generation for rolling, since Ring of Omen's charges grey health instead of stamina)
Hardcore Metal Band