The flaming guy that bursts out of the refrigerator in RE4 kicked ass.
Also, the regenerators and the "what's-it" in the burlap sack...
RE4 had a lot of inventive scares that revived the series. Another one of my favorites was returning to the church a short time after defeating El Gigante, and seeing the dogs for the first time. I said, "oh, hey, my dog is here." Then it pounced on me and I was frantically mashing away at the buttons to get it off. It was not the friendly dog.