That's the question The Economist tackled recently. It evaluated 127 cities around the world on a number of factors, which, according to the Times Online, include:
The methodology reflects the Economist’s belief that the cost of being in a city is no longer the only factor. Many business travel indices rank cities on the basis of average per diem rates paid to business travellers visiting the city, given that it is the traveller’s company who is footing the bill.
Three Canadian cities top the list: Vancouver, Calgary, and Toronto. The top U.S. cities were a little surprising: Honolulu (#5, OK, that's not a big surprise), Cleveland (6), Pittsburgh (11), Atlanta (13), and Boston (15). New York barely squeaked into the top 50 (tied with Madrid in the 47th spot). Anyway, it's pretty interesting. You can download the list from a link in the Times Online article.