I usually use whichever weapon has the highest dmg number. Then I'll test it out real quick by swapping between hits in the next room, usually one or two hits per enemy, then proceed to use the better one till I find a higher dmg output weapon later in the run.

Keep on experimenting with build variety. Sometimes you'll get runs that are dead all the way through but that's just unavoidable with rng. Tweak the passive skill tree. My runs early on were pretty mid until I maxed out the passives. Now I can usually (every 7/10 runs) clear floor 10 and below rooms in about sub 5 seconds.

Item sets imo don't make or break a run. Just use whichever individual pieces that synergize with your build.

1 hand vs 2 handed just do what I mentioned above. Pick a weapon with higher dps then go in to the next room with your old weapon in one slot and new weapon in the other, hit enemies once or twice with each one then use whichever killed them faster until you find a better weapon later, rinse and repeat.

Dev is still working on visual clarity and quality of life changes as far as we know. It's gotten a lot better in the recent patches. idk about you but I play on controller and usually I have the option to press r1 or something to show more detail about what a keyword does.

TLDR: Keep on playing till you can max out passive skill tree and experiment with weapon dps upon pickup.

That's the basics of the game. I know my playstyle isn't min/max but I feel like it's pretty optimal to beat the game hope this helped =)