Like J1m mentioned, probably your stumbling point is not enough defense. You almost always want to hit as many elites as possible though, since they're your most reliable way of increasing your power (Better card rarity in their rewards and of course the relic which can really kick your deck into overdrive) and by taking elites you can strengthen yourself so you can take elites easier and then snowball until you can stick your thumb up the boss' ass. That's generally a no-no with the potential caveat that sometimes, SOMETIMES in high ascension it's worth trying to avoid elites so your HP has a more comfortable buffer against the boss. Priority cards across the board are Acrobatics, Prepared, Alchemize, Tools of the Trade, Burst, Backstab, and Flying Knee. For Act 2 I try to focus more on getting spike damage, debuffs, and poison, and I avoid elites as best I can.
Generally take on Elites for Act 1 although those sentries sometimes really fuck me. I tend to focus on shedding basic defends and strikes and gaining defensive cards for Act 1, poison or spike damage as a secondary priority. Obviously I'm doing something wrong, but am having difficulty seeing where. I won my very first run with the Ironclad and my 2nd attempt with the Defect, but I cannot make any headway with the Silent after like 40 runs. I've also ignored my responsibilities as a parent to play this game while "taking care of" the baby and letting my wife sleep ("eh, he's 3 feet away from all electrical outlets, I can squeeze in a floor or two"). I picked this up during the sale last week and have already sunk nearly 40 hours into.
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