Someone out there hates the character and wants him ruined, locked away, or dead. The value of the Hindrance depends on how powerful the enemy is and how often he might show up. A Minor Enemy might be a lone gunslinger out for vengeance or a betrayed brotherhood that’s deadly but appears rarely. A Major Enemy might represent powerful authorities, a band of outlaws, or a single very powerful and relentless rival.
If the enemy is one day defeated, the GM should gradually work in a replacement, or the hero may buy off the Hindrance by sacrificing an Advance.