I played through P3P my first time as the girl, and I didn't feel like I was worse off for it. The big changes are the social links (if you don't know what social links are...by interacting with various people, you become closer to them, which allows you to make more powerful personas...it's all explained in game). If it's your first time though, you won't notice that they're different, they'll just be normal to you. The main plot points are identical, just gender-swapped.