Played through a few games, finally ended up beating the first Ascension with the Defect after creating some sort of build that basically became nigh-immortal after the first three turns. Here's the build for power cards (some of which were acquired via other power cards lol):
The melting green donut (and his buddy that died earlier in the fight) ended up getting some good hits in early on, until the block/lightning loop sphere started generating like 100+ block every single round. This was especially disgusting when the attack came around that provides 3 attack per all block orbs channeled in the fight (which of course was a shit-ton). Getting to this point in the game, where you essentially break the fuck out of it, is routinely the most fun I get out of it.
It's also worth noting that I chose the artifact after The City that provides you with an additional energy every turn, but prevents you from seeing the enemy's next moves, which nearly killed me several times. I personally feel like Darkest Dungeon gets a little too punishing; the payoff on power never really came around when I was playing it. It's nice to earn a kick-ass build and feel like you deserve it.