We are 5 in a 3BR 1800 sq ft and it is too small. I have hobbies (sewing, woodworking, guitar/singing) and I like the kids to have hands on stuff to do--arts and crafts, puzzles, legos, piano (upright), and robotics. We don't have a good backyard for the kids to play in, so they spend most of their time indoors, and when we have people over for dinner, it tends to be large groups sometimes up to 20 people (in past apartments, we have actually shoved beds into closets and set up tables in the bedroom!). I will also probably work from home after the kids are all in school. 2200 sq ft seems to be the sweet point for us, but most important is the ability to have guests (especially my parents) stay with us which we probably do about 6 weeks out of the year. Sometimes the guests have families of 5. Most of these guests cannot afford a hotel or are too frugal to visit us if they had to pay for one.
I would love to have a 2500 sq ft house. While it would seem extravagant after how we're living, it would take a lot of stress off of our marriage. I was coaching a robotics team this fall and had a 4'x8' playing field on the dining room table for 3 months. We ate dinner at the crafts table which is a small preschool-type table. My husband did not fit in the kids' chairs. He was very gracious about the whole endeavor, but having a room dedicated to these hobbies/endeavors would be much better for us.
A lot of sq footage is also lost in the layout. Stairs, balconies, and hallways can take up square footage space that do nothing, so your 2500 sq ft house could be just as usable as someone else's 2100 sq ft.
My bigger concern about your house is the flood issue. When I was a child, parts of my desert city occasionally experienced large amounts of rain and the news showed houses under water up to the eaves with people boating around and getting airlifted off of roofs. I assumed this was a regular occurrence (I'm certain it happened multiple years) and couldn't fathom why anyone built there knowing it could flood. We lived higher up than these houses, but during these rains, even our backyard was a river. So, my biggest concern with your house is the question of what level of flooding will you get. Basement flooding isn't the worst thing, but if your house has the potential to be completely under water, I am worried for you.