It is a bit of a challenge going through on Nightmare difficulty, it also makes it more challenging due to your health decreasing 5 points every few seconds until it rests at 25. On the plus side you start the game with the Soul Cube, which can come in handy in tricky situations. Another plus is the option of being able to save at any time, this will help greatly during a Nightmare playthrough.
I believe the enemies still have the same health but they do inflict more damage, plus with the fact you'll constantly be on 25 health, unless you use the Soul Cube during a tricky situation. The enemies deal out more damage, so most hits will be instant death unless you get hit with splash damage.
Completed Retail (100%): 68
Completed Arcade (100%): 25
Most Recent 100% (Retail): Fifa 14
Gamertag Updated from DarkSeraphim198 (21st Jan. 2011)