The Best Explanation: Another Hastings! Melissa has always been on the inside when it comes to dealing with the "A" game. She was tangentially involved in the N.A.T. Club, and when the show starts, she's engaged to Ian. She loses him, of course, and then she remains close to Wren (another previous "A" suspect) throughout the seasons. Melissa is constantly frustrated and angry with Spencer and all her friends. It's never been a secret that she dislikes them. At one point, she claims she's trying to protect Spencer, but that just confirms she's got a lot of secrets we don't know.
There are more reasons to suspect Melissa is running the show. Maybe she wants to avenge Ian's death. Maybe she wants to make Spencer and her friends pay for ruining her life. Maybe she hates the fact that Spencer isn't a true Hastings. No matter what the motive, Melissa is the perfect candidate for a menacing, cruel person who just wants to make the liars suffer.
The Most Damning Evidence: One sentence: Melissa is the one who kills Bethany Young. This casts Melissa as a person who has something to hide, who has a dark side, and who has murderous tendencies. Melissa has been tangled in nearly everything. She's so involved in the night of Ali's disappearance. She always seems to have a hand in the latest trouble. Logic would argue it's because she's the one running the show.
