While all City of Villains players benefit from the game’s software physics created by the AGEIA PhysX SDK, players with PhysX Accelerator cards will experience some 10 times the number of particles displayed in physics-based events, resulting in an even more immersive experience. For example:

- Mayhem Missions, which are set in a destructible environment, have destroyed objects taking greater advantage of the physics effects, such as a newspaper vending machine which, when blown up, shreds thousands of particles of paper around it.
- Physics particles can be affected by external forces. For example, the shredded bits from the newspaper machine linger in the air only to be blown away by other explosions.
- World geometry will be retrofitted with reactive physics effects, such as leaves being dropped from trees when a Power Blast is cast nearby.