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A lot of times you'll get 1 or the other stuck on something unfortunately and there's not much you can do about that other than choosing more time consuming paths
But I had some good survivability in Dark Bum and the Glowing Hourglass.
I really dislike this character.
Good job!!
I did have trouble in my first few runs, but now I can consistenly beat runs with them, which was caused by the following change in my playstyle:
DO NOT SPLIT THE DAMAGE / TEAR EFFECT ITEMS.
You will get your butt handed to you with 2 mediocre DPS-dealers in the womb, if not earlier.
Let Jacob take all the DPS upgrades and fully focus on controlling him, while dragging Esau right behind you.
Another benefit of this strategy is that you can just hold your right trigger (or CTRL on Keyboard, i think), to clear out tight spaces or nasty hosts like you usually would.
Try keeping Esau healthy (He should get the defensive / utility items), and view him as a nuisance, not as one half of your damage AND a nuisance.
EDIT: Go for angel deals, be very very careful with flight, if you can't get it for both, it's super easy to bump into a corner and/or get seperated that way.
Just had ANOTHER great run defeated Blue Baby and got really lucky with a Void portal after the fight and went for Delirium and beat him too with full HP and Percs pill for both characters!
As you said splitting up items is not a good idea except for HP, I just beat two runs in a row like this while up until today I only had failures.
Edit: Just beat the Beast and unlocked Tainted Jacob, I don't know what to say... it must be my lucky day.
If you know, what some enemy pattern shoot cardinal directions, quickly reposition yourself that way, so you both characters make formation that will be easy to dodge. On bullet hells, focus more on yourself, not shooting. Since you shoot both characters, you can still deliver good damage. But safery first.