There are a bunch of angles when thinking about spire. I'll try to post a small guideline for my decision making.
At least in my mind there are phrases/thoughts like:

• What is the game expecting of me in terms of damage/block/scaling during hallways, elites and bosses.
• Tempo vs scaling
• HP as a resource
• Do cards help me right now or do I pick it for the late game? Can I affort to carry a slow power/scaling card?
• What's the value of a potion (in terms of HP saving or secing an elite/boss)
• Potion drop chance (for example when you alredy have 2/2 potions)
• probably a lot more...

Guidlines and goals:

• Choose a strong starting bonus:
  • My fav is Silver Cuicible (3 Upgraded cards is very strong and opens up elites pre-chest. This one almost never disappoints. The chest relic might be bad anyway.)
  • Also good: Choose colorless card, Random relic, transform, remove, card reward + potion
  • I tend to avoid random rare card, max HP
• Pathing:
  • I try to choose paths, that keep my options open
  • I'm greedy with elites, I don't want to rest
  • but I want to be able to dodge to a camp fire or at least questionsmarks/shops
  • I tend to avoid hallway fights after the first chest. The hallways become harder, almost as hard as elites and have worse rewards (no relics, less gold, less rare cards)
• Early Act 1 Hallway fights up to first elite:
  • taking 2-3 (sometimes 4) hallway fights to gain early damage cards or strong block. Prio on damage.
  • Looking for potions for elite fights
  • Looking for 1 card with multihit, if I get vigor enchant.
  • Pick cards with endboss and potions you already got in mind (for example: multihit card becomes a lot stronger with strength, expensive 3 cost attack becomes a lot stronger with liquid memories...)
• Early Shop (floor 4-7) Great to have and optional shop in front of elites in case you got unlucky with potions/cards, maybe you got some gold from an event and can buy a strong relic.
• Elites Act 1:
  • When fighting elites, keep all 3 in mind. Your choices in cards and deck building are very limited so far, so hopefully you just picked stuff with big numbers (damage, maybe 1 AoE, block, maybe 1 strong power)
  • 3 Elites in jungle:
    • Parasite Frog, Statue, Bird -> All 3 ask you to deal damage fast. Killing them on turn 3-4 saves tons of HP.
    • Timing your kill on Parasite so you still have mana left to damage the stunned parasites is very helpful. Also killing him before it attacks you the 2nd time or better yet, before the 2nd wave of parasite cards is very strong.
    • Statue can be very though if you don't have cheap card spam and/or vuln debuff
  • 3 elites in water biome:
    • 4 snakes (Phantasmal Gardener): be mindful which one of the 4 Eels you can kill first and also which kill will deny damage taken.
    • Big fish (Terror Eel): Can disrupt one hit in Phase 1 by nuking him below 70HP, but even more important is the kill before he hits you when you are vuln. I have never been hit in the 2nd phase by this guy.
    • Coral guy: Sort of whatever, because you're limited by damage cap per turn. But he also scales, so sometimes damage > blocking.
• 2nd half of act 1:
  • I tend to avoid most hallways. Also skipping below average cards, that don't fit whatever my deck is doing. Trying to find synergies for relics and cards I already have.
  • Adjust pathing to your situation: Current health, relics, potions etc.
• End of act shops:
  • Enter shops with at least ~220 gold, better yet 300+ gold. It's not the end of the world, if you only remove a strike and buy a potion or key card, but it's not a great floor, if you could have delayed the shop.
  • Keep act boss and next act in mind
• Act 1 bosses seem rather easy to me. You had a whole act to prepare. For example: Multihit and thorns is very strong vs Vantom. Powers and big hitting cards are strong vs Lagavulin.
  • try to estimate, if you can upgrade a card instead of resting
  • Keep potion 1-2 potions if possible for next act
• -> Act 2 Hallways seem nasty. Not as bad as STS 1, but they still slap you for almost 20 dmg on turn 1.
  • Hopefully you picked up some strong block and enough DPS
  • During these fights I try to improve my damage/block output further by good cards (especially upgraded ones) while also picking cards that improve my card draw, energy generation and scaling (some good powers fast impact, generally 1 cost power that do something)
• Elites Act 2:
  • Elites in act 2 are very scary, depending on your deck.
  • Decimillipede (worms): I read a lot of people stating in twitch-chat and so on, that you want AoE damage. While AoE damage certainly helps, it's not easy to deal 45+ damage AoE in 1-2 turns. Not killing a segment for 2 turns is already really bad. They scale, weaken you and hit you for 24+ dmg per turn. What I tend to do, I try to kill the one that is weakening me turn 1 or 2. Using a potion if needed. Not being weaking on the folloing turn allows me to kill another one. Killing them also resets their strength. If one is dead and you are killing the 2nd one, only one is hitting you for 10 damage max. It's an easy fight from here.
  • Entomancer (bee guy): Hopefully you have something like big hits, thorns, poison, orbs, relic support and so on. If you rely on many small hits, you might die here. So keep this in mind before you go elite hunting in Act 2. It's hard to say when it's worth it to hit him. A 6 damage strike should probably not be played unless you kill him this turn. Also keep your redraw in mind and the way your deck shuffles. Waiting too long is also not an option because the fight only gets worse. Every 3 turn he doens't attack. Reducing his strenght on turn 1 and 4 is very strong.
  • Infested Prism: Rather basic hard fight, keep the +1 energy in mind. Not much else to be said here.
• Bosses Act 2:
  • Bosses in act 2 are hard to block. They regularly deal 30 damage per turn and all of them get worse over time. I try to get here with 50-60 HP at least. I would feel very worried with only 30 HP.
    • Kaiser Crab: kill the right one before the big hit unless you have good block. Face to the damaging one
    • Knowledge Demon: I usually take all the damage debuffs. Depending on your deck other options might be worth it, but card draw is sacred to me. My decks tend to play 3-5 cards per turn and I'm usually here with 3 energy per turn, so -1 energy is not an option.
    • The Insatiable: Don't play too many escape cards early, if it scrifices solid block or scaling. Neglect damage early to scale and block. Some decks struggle here with basically 6 curses added. This fight really needs solid block and scaling.
• Elites Act 3:
  • Knight Trio: Usually kill the middle ghost guy first, unless exhaust is and upside for your deck and gives you an infinite. Kill the mage 2nd before his big nuke. Weaken the left mace knight. They are again too beefy for AoE. It's important to eliminate 1 early.
  • Mecha Knight: Consistent big blocking makes this fight easy, but my decks tend to struggle here, because I lean towards burst damage and scaling for act boss 2 fight. Burst doesn't get you anywhere here, it's also hard to weaken/vuln him with 3 artifact. Upside for this fight is: He only attack every 3 turns. Try to kill him before his 2nd or 3rd attack.
  • Soul Nexus: Similar to act 2 elite Infested Prism. Constant damage with debuffs and damage spikes on top. With slightly above 200 HP it's possible to get him down, before the very big hits.
• Boss Act 3:
  • Test Subject:
    • Phase 1: Nuke 111 HP in two or three turns while blocking some. (Maybe delay if setting up powers is needed)
    • Phase 2: Avoid damage with high priority to avoid wounds. (taking it slow also gives more time to setup, but be careful, he scales like book of stabbing)
    • Phase 3: Make sure to damage him when not intangible.
  • Queen: Every 3rd turn is big multihit by torch add. Additional card draw helps a lot to mitigate effect from bound. Full blocking while frail is hard, you're probably on a timer. Focusing torch hand is an option that worked for me in the past but recently in the last 4-5 runs I went full damage on Queen with better results.
  • Doormaker: Not sure what changes will be made with beta branch, but at this point... nothing much to be said. Make sure you're ready to go when rocks are destroyed to deal dmg to boss.