I think the three keys are:
1. Direct flight
2. Renting an apartment (
www.vrbo.com is a good site to check out) rather than a hotel so you can cook for finicky kids...and save $$
3. Finding a city that you an stay put in for a week or can do easy day trips rather than dragging people around from place to place. So it has to be interesting, beautiful, kind of big, diverse, etc.
Some good cities with those criteria:
- Barcelona (We did it and loved it)
- London
- Paris
- I second Prague even with no direct flights!
- Lake Como region in Italy
- Rome
You can do it! The flight over is pretty easy as it's overnight and the kids will sleep. The trip back can be a bear but you'll survive with lots of walks up and down the aisle. Good luck