first off, enjoy the effective public transit... something we've never seen here in Columbus. I'm a beer and movie guy, so sorry if most of my suggestions lean in that direction.
Bloor Cinema - will re-open this fall under new mgmt, the area around has some great dive bars... if you're in town for the film fest I envy you.
http://bloorcinema.com/
C'est What - brewpub with an amazing selection of in-house microbrews, in the business district around a bunch of really fancy establishments
http://www.cestwhat.com/
Queen St. West - great boutique/eclectic shopping and eating
Toronto Island Area- I've a friend who has went there for writer's retreats and talks about how peaceful it is where she stays- but I've never made it down there.
Rogers Center/CN Tower/Steamwhistle Brewing - very touristy, but I like baseball/towers/beer so it was a win/win/win
from bathurst (w) to parliament (e) the lake (s) to bloor (n) there are 7 breweries, and the architecture around the University of Toronto is quite the mashup west of Yonge between Bloor (n) and College (s)... I believe Chinatown is on College/Spadina if memory serves correctly so plenty of eating/grocerying opportunities there as well.
Yonge St. is like High Street in Columbus, it runs the whole town North to South and different neighborhoods have different offerings along the way- hard to make any specific recommendations, I've always found something new each time on Yonge.
Eaton Center is kinda shiny, but I can't really say I enjoyed anything IN the complex... we have much of the same stuff at Easton/Polaris... but I have found good restaurants and book stores on the periphery.