We were in the same predicament 5 years ago. Only we had horrible neighbors (a 7 yr old firebug!), so we definitely wanted land AWAY from people.
We went from 1750 SF to 4200 SF, and I would do it again in a heartbeat! The key is to find the right floor plan for you. It took a lot of looking on our part - we ended up buying a home that had been custom designed for the original owners. Meaning it has an unusual layout, but none of the features we didn't need (like a formal dining or living area, which we'd never use). Every inch of our house is used. Don't settle for a floor plan with wasted space, that will definitely make your life more difficult.
As for size, the upkeep is actually LESS than at our old house! With the new house, it's not as old (7 yrs vs 25 yrs), and it's better built, so there's less dust and cobwebs. With more space, I find that we also use the rooms a lot less - in the old house, the kids could play in the living room or their room - that's it. In the new place, they divide their time between the living room, gameroom, their rooms, my craft room, and a computer nook we set up. It just doesn't seem to get as messy since they're not spending ALL DAY in one room. I would have to clean the old place 2-3 times weekly to get it presentable, with the bigger house, I can easily let it go every 2 weeks and it still looks fine.
If you do get acreage, it doesn't mean isolation. You can get a decent sized lot - 1-3 acres - which isn't bad to maintain and you still have neighbors close by. Our neighborhood is all 1-5 acre lots and there are tons of kids around. Sometimes you have to drive to their house, but it's also nice that way - you always know who your child is playing with, not the "bad seed" of the neighborhood! We ended up with 3 acres that are completely fenced in. I love that I can open my door (front or back!) and tell the kids to go play and know they're completely safe out there. They're both boys, so the "exploring" the natural terrain has been a blast. We only maintain about 1 acre of the property and let the rest remain wild, so the upkeep is actually less than at our old house (which would get you a citation if your grass got too long, so you always had to mow weekly; last year, when we had that drought, we only had to mow ONCE at the new house!).
I agree with the others who said look around. Check out what the neighborhoods offer, ask other moms at school if you're curious about a certain area, they'll usually tell you the truth. But don't commit until you've found the perfect layout for your family.