Tips/Jacob & Esau

Tips
Jacob & Esau being two separate characters brings out some pros and cons. Jacob & Esau can be hard characters to play as, even with the benefits it brings.

On stats, the brothers are very similar. being the same on speed, range and damage multiplier. We'll skip speed, since any speed modifier applies to both twins, with little exceptions like Libra,

In base of these stats, the player should give priorities to which character should get said item, in order to avoid having one character underpowered. Jacob has less damage and shot speed, while Esau has negative luck, less health and less tears. Even though both have the same base range, Jacob's shot speed reduces his effective range.

Apart of that, speed and range are the same as Isaac, so individually there's no much difference from playing Isaac.

They start without any item. So you should start building up from the start if possible.

If a room contains two item pedestals it is possible to pick up both items. Simply separate, line up and walk into both item pedestals simultaneously.

Adapted controls
The problem doesn't lay on movement and aim (WASD and arrows), since both Twins share those. The main changes are made so Esau isn't limited.

Practice with the use of Q key, which changes from pills/cards to Esau's Active item. That forces you to consume any of these without even checking. This makes cards unpredictable and unreliable since most of their effects applies to the actual room or teleports the player, while you have to remember each pill color to avoid the negative ones. CTRL allows you to separate Jacob from Esau, which can be helpful to resolve puzzles, pass through narrow shots, or keep Esau away from damage.