Kim Possible
When she's not avoiding mean girls at school, Kim Possible is fighting the evil crime of her small town (of which there is quite a lot.) She, joined by her best friend Ron Stoppable, is on a mission to save the world and get through her high school experience. Her biggest rival was Dr. Drakken, but more so his sidekick Shego, who had the same abilities as Kim, but malicious intent. It started in 2002.
The Grim Adventures of Billy and Mandy
This was one of Cartoon Networks weirder show pitches. Billy and Mandy (2000) are a pair of young friends (barely) who befriend the Grim Reaper after defeating him in a limbo contest. His punishment for losing is befriending the two weird kids. Mandy's bossy and mean nature if offset by Billy's curious attitude and goofy sense of the world. Together, hilarious escapades are bound to happen.