I played a game as Sebille. You don't -have to- kill the lizards but you do get optional dialogues with most of them to initiate murder. Aside from a few Sebille-story essential NPCs though you don't have to go the psycho-murder route if you don't want to, but then why play that origin character? She's made to be a psycho!
In general you can murder anyone in the game (except for Malady) and still continue the story. you will miss out on some quests that way, but hey -- if you want to play 'the ultimate psycho' I applaud the game for allowing you to do that.
