A lot of what Dusk Golem already said. Harder enemies (the hunters are way harder than lickers, lots of packs of dogs, the insect critters), more zombies (and a lot more instances where they come from behind as well as in front of you, or new ones break through the environment in cramped corridors), harder bosses, scarcer healing supplies, way "harder" puzzles, and nemesis. It gets easier after the clock tower stuff tho since you have a huge arsenal by that point, but every classic RE game gets easier towards the end.
I actually think Nemesis is easier than Mr. X. You can always run to his weak hand, whereas Mr. X tends to catch you with the quick hook if you try that.