but why Natalie?

As Brenda herself states: You weren't driving, but it was your car! And you were there, Natalie!

And on top of that Natalie makes out with Brenda's new love interest, I guess that was enough reason for her to get crazy on Natalie, but still doesn't really make sense why she kills all those people who weren't even her real friends in the beggining, she should've killed her right away, for some reason she just decided to play more with Natalie.

I assume she just inserted herself into the life of the one who was more receptive (or naive) when she transferred to Pendleton.

Revenge doesn't make much sense for a serial killer anyway. She's killing blameless, innocent people to make someone who she blames for killing her innocent boyfriend suffer before dying.