I would recommend the Sutton Place Hotel on Bay & Wellesley as it is un des hotels de choix for Hollywood types during the Toronto Film Festival and is across from a very good restaurant, Bistro 990.

But perhaps most important, it is only a 30-second walk outside (br-r-r-r in December! ) to the excellent and safe subway stop on the Yonge Street line at Wellesley & Yonge. It is also walking distance to the University of Toronto, the Royal Ontario Museum and the ritzy shopping district of Yorkville.