-( Story related, cannot be missed )-
Mz. Ruby is going to be a frustrating fight (for me, she was). You won't have much of a problem in actually hitting her; the problem is more in getting to her. She casts hexes at Sly as he slowly makes his way to her (by turtle, by spire, and by mosquito). Pay attention to the symbols she's sending (O, Square, X, and Triangle) and press the appropriate buttons at the same speed she cast them to get up to her. You will have to go through three different "Simon Says" stages to hit her four times (if you die during any of them, it will count the first hit every time, so you just have to hit her the three other times to win).
You will unlock the following trophy along with this one: