It's difficult to defeat the epic bosses because they are well epic! But it's not an easy task, and if you want to succeed in defeating the epic bosses you will have to use specific heroes.

Elektra (Chapter 2-3)

• Use hero: Black Cat to defeat
• Elektra Drops: Grecian Sai – counter and bleed effect

Magneto (Chapter 4-4)

• Use hero: Storm
• Magneto Drops: Magnetic Field Generator – creates shields and when the shields are removed the ally gains an extra turn

Dr. Doom (Chapter 3-5)

• Use hero: Spiderman
• Dr. Doom drops: The Doombringer – Debuff an enemy and raise your agents stats

Loki (Chapter 5-3)

• Use hero: Wolverine
• Loki drops: Norn Stone – Increase all the agents's stats

Doctor Octopus (Chapter 6-3)

• Use hero: Black Widow
• Doctor Octopus Drops: Electrostatic Arm – Attacks will also shock enemies; enemies with negative charge receive extra damage

Have in mind that in order to actually get the Epic Bosses, you will have to complete all the missions in the chapter.