The main way to create EMC in early game is by farming or mining. The materials can be placed either into a Transmutation Tablet or Energy Condenser to convert them into EMC, which can then be used to create other substances. (Note: Some of the best ways to get EMC in early game are farming sugar cane the Vanilla way in large amounts, or using Industrial Agriculture to farm pumpkins or melons.) In late-game, the most common way to get EMC is through Energy Collectors and Antimatter Relays.
There are known ways of generating EMC by using bugs or the official way.
One of the most commonly known bug is because Macerators can make 5 blaze powder, and it takes only 3 to make one more blaze rod, all the excess will be used to other things.
See the article Alchemical Math for a complete list of items that can be transmuted or converted into EMC.