Also, I'm really surprised SNES Dracula X has been mentioned a few times. That game is such a cakewalk for me I find it surprising that people have such difficulty with it as to consider it one of the harder titles.
It depends how you decided to complete the game.
Dracula X on the normal path where you fall in stage 4 and traverse the catacombs is straight forward.
Playing the game where you fight the white knight and save Maria and Annette is much more difficult.
For one thing, you have to finish stage 4 with no sub weapon (because of the key) and you can not fall into the pits in an area ripe with medusa heads. As soon as this happens you need to start the game again, or use a password which let's you start at stage 4. Secondly, if and when you beat the knight, you need to pass through a series of rooms which are also very easy to fall off and ghosts keep following you. Then you need to get to the right room and use the key to free Maria.
If you save both girls, you have to fight death, who is harder than Dracula. (Drac isn't easy, but he's easier than people think)
I would say the hardest are:
CV 3
Haunted Castle
Bloodlines (mainly the later stages)
CV Chronicles
Dracula X (saving both girls)
Cotm/ OOE on Level 1 (either mode)