Runes affect the game in different ways.

There are two ways to get rid of enemy runes. First, there is Rune Smash, which costs 4 Mojo, and gets rid of ALL runes, including the player who uses it. Sly Rune Smash, which costs 6, gets rid of only the enemy runes, but is priced too high for 3 and 4 Mojo heroes to bring (and not a no-brainer for 5 mojo heroes).