We just came back from our first vacation with the girls. I don't know how old your little ones are, but for us it was a LOT of work. We had fun, but my dreams (hallucinations?) of it being a nice relaxing vay-cay were dashed. The biggest problem we had was trying to do things around the girls' nap schedule. They are morning nappers at home. So we'd wake up, do our regular routine (dress, breakfast, mom & dad get ready) and it would be naptime. We would put them in the car and they'd nap for 20 minutes or so, as we drove to whatever destination we had picked. That just wasn't enough for them. So in the afternoon when we were having lunch (in a restaurant), we'd have a meltdown. We couldn't really let them have their morning nap, or else we would have spent the entire day in the hotel room. One problem, which was poor planning on my part, was the hotel was a little far away from the attractions we wanted to go to. We should have picked one where we could walk back when the girls got tired in the afternoon, and we could have made lunch in the kitchen. Again, bad planning on my part.
They actually slept pretty well at night. And babyproofing wasn't a problem, we just kept an eye on them (much easier when there are two of us, rather than just me like at home since I'm a SAHM). And it really was fun. We were in Amish country, and the girls liked seeing the animals etc. It's fun to watch them see new things.