Which semester is going to be the hardest depends a lot on your individual program. In my program 3rd and 4th semester are really hard, and 1st and 2nd are a bit easier. For my friend at his school, 1st and 2nd are considered the hardest and 3rd and 4th are easier. It just depends how your program is set up.
Granted I'm only in 1st semester, but so far nothing has been "hard" persay, but it's a lot of information thrown at you at once. I think A&P and chem were harder for me than any of my classes this semester, but in nursing school
you're introduced to a different way of thinking and I think it's just hard getting used to nursing school, because it's much different than your pre-reqs. I study at least a little bit each night, and I go to school 4 days a week.