In Season One, the mystery was the murders of women connected to Sookie's brother. Maudette, Dawn and then finally Amy all are strangled. These all happened after they spent time with Sookie's brother. The Sheriff thinks Jason (Sookie's brother) is the killer, until his and Sookie's grandmother is killed.
Jason soon becomes addicted to, "v-juice", vampire blood. He meets Amy, another v-juice addict and they begin a short relationship. Their relationship finishes when Drew decides to murder her. At the end of the season, Jason joins the Fellowship of the Sun, which is a movement against vampires.
Here is a clip I've found on Youtube, it's a preview of True Blood Season Two: