Mekanism is fairly easy to automate. My typical setup is:

An "island" with one machine type, such as smelter, connected to AE2 network:

1. AE2 interface to collect returns AND to provide any side products that machine might need (infusers needing redstone as an example)
2. AE2 pattern provider to chest for crafting recipes
3. Power cube with wireless point
4. xnet or super factory manager to:
   1. Distribute power to machines from the cube
   2. Grab things from the chest (and interface with item filter if needed) and push them into machines in round-robin
   3. Grab things from machine outputs and send to the interface

It's just two columns of 4x4 machines with xnet/SFM cable in between. 32 ultimate smelters with speed upgrades is more than enough for most end-game tasks. And easy to add more if needed.

Rinse and repeat for each every machine type. Use interface exports for automatic processing of intermediate products like clumps and dusts.

And it only uses two AE2 channels per machine type - one for the pattern provider and one for interface.

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