When talking about drugs, people are said to be tweaking when they make uncontrollable movements which they have no control over. This form of tweaking happens to people whom abuse hard-drugs such as Amphetamines (Cocaine, crack, meth, etc..). Some common effects from tweaking on drugs include constant itching as if the user has bugs under their skin.
When someones acting out of the norm, such as picking fights with random strangers, people refer to this as tweaking. In Bobby Shmurda's "Hot Nigga" song, Shmurda said "F*ck with us F*ck with us and then we tweaking ho - Run up on that n*gga get to squeezing ho."