The hardest for me for was going from 1 to 2. But my first two were my closest pregnancies, also. With one kid, it's just not that big of a deal, you can still pick up and go pretty much, but when you've got two in carseats and diapers, it just changes everything.
However, my house didn't really fall apart until after #3 came along.LOL I kept it under control until she was a few months old, but it slid downhill. If it hadn't been for Flylady, we would have lived in chaos from then on!
Going from 3 to 4 was an easy transition, and 4 to 5 was even easier. But once you have older children to be extra hands (and I home school, so they are always around), it just isn't as stressful to have a baby. And, for me, I got more and more content to simply stay home. The biggest hassle is getting them all ready to go somewhere, but the older kids can help the younger ones. I usually only have to worry about myself and the "baby". Once the twins are born, I will only need to worry about them, and my toddler will be someone else's responsibility when it's time to go out.;-) And that's if she isn't taking care of herself by then; she's pretty independent.
So I will warn you that the ages between your #2 and #3 are a prime age for jealousy issues. Right around 2yo seemed to be about the worst time for kids to handle a new sibling. Three to three and a half seems to be a prime time, from my experience. They are old enough to feel that they don't need much babying, and can welcome a younger sibling with open arms. At 1yo, they don't seem to care too much about a sibling, so that works, too, if you can handle having two babies!LOL I've never had a spread longer than 3 1/2 years, so I can't speak to that.