I've only tried nWoD once, but I'm going to echo the lethality of it for most characters.

If you're planning to run a mortal game, tell your players beforehand that engaging in a stand-up fight means that somebody righteously screwed up somewhere. You have a finite number of hit boxes and even a knife held by a random hobo can totally mess you up.

Balancing bog-standard humans against supernatural creatures is very difficult, especially if the humans don't have very specialized knowledge about the weaknesses of the supernatural creatures. There's a reason that Van Helsing used to stab up his foes during the daytime whenever he could pull it off.

If anything, I would suggest running each encounter as a puzzle, with varying degrees of a "right way" to go about doing it.