That sucks that the grandparents or family won't babysit for 4-5 days while the two of you vacate. Our two little girls are virtually the same age as yours (3 and 4.5), and we are very lucky to have two sets of their grandparents and some aunts that fight over who gets to take them for a few days. So we have done a couple of quick trips to vegas this year sans kids and we are hoping to go to Mexico this winter (if swine flu and company related quarantines aren't an issue).
But that doesn't solve your problem. Two things come to mind. First, reconsider cruises? DW gets very seasick easily, but had no problems on our last week-long cruise when she kept herself loaded up on non-drowsy Dramamine, and there is chewable Dramamine for the kids. Side effects were minimal, but consisted of mild drowsiness occasionally (I think that's why they took so many naps
). I have heard the patch works even better. But it could be bad if you figure out on day 2 of a 7 day cruise that the medicine isn't working. Our kids liked the Kids Crew childcare onboard and it is free most of the time, otherwise fairly cheap per hour (such as when you are in port).
The second idea would be tag-team vacationing. Go with another couple that has youngish children, and trade off babysitting time. You take 8 am till 4 pm on Monday with all the kids, then the other family takes 8 till 4 pm on Tues, then repeat. Maybe work out evening babysitting trading on a case by case basis. It doesn't get you completely kid free, but it comes pretty close. Not sure if your wife is like this, but my DW has separation anxiety from the kids and starts missing them before the vacation is over. This arrangement would prevent that.
I feel your pain though - we really enjoyed the short vacations away from the kids where you don't have to worry about being responsible for other human beings. Best of luck!