I usually wouldn't endorse this sort of thing, but looking at the enormity of the site, I think it could work as a good place for a huge secondary downtown mall.
Now, before I get shot, hung up and left out to dry, let me suggest that such a thing should only go forward if you could get a superior architect, and the place would be beautiful and exciting in it's own right - especially on the street and not only because of what is inside. If people aren't happy to walk along it's Queen's Quay face on it's own, then it should be a no-go.
The site is walled off from the city along it's entire north face by impenetrable traffic infrastructure, which causes a good deal of noise and vibration. No new links will be being made through this. So -
People would like to walk from Harbour and Yonge to Sugar Beach, but the walk is currently drab. With the communities planned for East of Sherbourne, anything that will help people get from the Yonge-Union central area eastward in comfort could be helpful.
A long interior enclosed diagonal walkway from Yonge-Harbour to QQ-Sherbourne could be popular.
The streetfront along QQ would have to be variegated enough in appearance, of moderate height and made lively with retail and residential, that'd be fine as an exterior street independent of the mall behind it.
There's be rooms for some ultra-tall towers at the Yonge end (the Toronto Star building could be left as is, or demolished and re-incorporated into a new 1 Yonge) with a foundational building size that tapers down to small midrises toward Sherbourne.
It could easily incorporate the planned for cosmological centre, new planetarium, omnimax, IMAX, a waterpark, a year-'round park, etc., etc., all sorts of fun stuff.
It would be a lot more roomy than the Eaton Centre, currently usually jammed to capacity.
It being a few steps away from a subway stop would be a slight depressant, but with a main entrance on Yonge, at the foot of Yonge, it would have a strong chance of success - esp. from the new east and west waterfront neighbourhoods.