Find what works best for you. I originally ran 42X16 here in Louisville which is pretty flat with only moderately sized hills. But I eventually went to 48X16 because I find it to be the perfect compromise because it allows me to keep up with the typical roadie and/or paceline on the open roads yet it's low enough to make sprinting from light to light through the city streets, storming into head winds coming off the Ohio River and climbing the hills a relatively casual affair.