Rochester is a city that has some interesting sites and attractions, but almost without exception, you will need to have a car to experience the best that the area has to offer.  Downtown is starting to develop to its potential both residentially and recreationally after some very dormant years but most of the hotspots are still spread out with either a very short drive or reasonable cab ride.  One good area is the East End with the Eastman Theatre (music), Little Theatre (independent films), and many streets lined with cafes, bars and clubs.  The George Eastman House (film & photography museum/Kodak legacy) is fairly close - perhaps 4-5 blocks down East Ave.

Most rental car agencies are at the airport with the exception of Enterprise which does have other locations.

 If you have a GPS, bring it with you.  Most rental car agencies will charge $10-$15 per day to use theirs.   While the streets of Rochester aren't particularly difficult to figure out, a GPS is invaluable when trying to find something not on a main road. 

There is lovely countryside outside of Rochester with farms, wineries and natural attractions (Letchworth State Park- lovely gorge, the Finger Lakes) so it is worth it to get out and look around.