What are the good unlocks?

[Grunt]

With what character and what boss should I beat to get some strong unlocks? Or which challenges?

[jayhena]

rock bottom ; planetariums ; revelation ; the stairway ; birthright ; guppy's eye ; echo chamber ; dark arts ; spindown dice and the red key are the items that i'd consider the best to unlock fast

[skeleman]

check the character and challenges pages on the wiki to see what unlocks what. dunno what to recommend since you've already got what i would consider "good unlocks" judging from your achievements.

[kone]

Bethany's unlocks are great, get them. But do Jacob and Esau's unlocks asap because as tough as they are they have some of the most important, unique and fun items you can get in a run. All of them.
Some select helpful unlocks you might not have yet:

Cain - Mother - Guppy's Eye
??? - Mother - Eternal D6
Keeper - Mother - Keeper's Sack
Isaac - Beast - Options?
Lazarus - Beast - Astral Projection
Forgotten - Beast - Spirit Shackles
Bloody Mary Challenge - Sigil of Baphomet
Isaac's Awakening - Spirit Sword

[Random]

For the non-items unlocks the tainted characters Greedier mode reverse tarot cards and the Mega Satan unlocks (Horse Pills, Gold Pills, Golden Penny, Crane Game, etc.) Are also really good