Depends on what you have time for. Some of my favorite places to go to:
Indoors: RMSC hands down, LOVE the science center and the planetarium shows are great.
The Memorial Art Gallery...
Eastman House
Strong Museum (and stop and see Tad! aka Museum Guy
OUTDOORS: Any of the parks along the canal are beautiful. Greece Canal Park has a great playground.
Ellison Park is GORGEOUS (they have a doggie park there, too.)
If you can get down to Irondequoit Bay, there's the Bay Paddle Club and you could take out a canoe...also, the area down there is so pretty.
Seabreeze amusement park...couple of decent coasters and water park
Charlotte Beach...for a nice easy going couple of hours...very very nice. Grab a burger at either Schallers or LDR...which is right there beach side. Abbott's frozen custard...walk along the boardwalk and then nice walk out to the end of the pier...should be sailboats out...Also down there is The Pelican...which is right along the River for eats and/or adult beverages. The Charlotte Lighthouse is worth a visit. Little known secret..coastguard Rents out an apartment to college students/interns with them and usually the guys will give you a tour! But please don't laugh at our PORT...which was only a PORT for the Fast Farce...er um...Ferry. You can still catch a ride on the Harbor Belle, and I think right now the Nina and Pinta are in Port.
Hope you have a wonderful time!