Very exciting prospect.
I'm going to agree with Towers first suggestion a go with the Hobby Building. The potential is massive. Access from Lavaca and Guadalupe with prime street front on 4th and parking access on 3rd. Thy could revitalize the fountain/courtyard area and also possibly connect underground with the Republic Square subway station. You could get off work downtown, shop at HEB and then hop on the subway/light rail home. Amazing.
It would also have residential shoppers from the W, the Austonian, Republican Square, 6X, BBVA, Zaza, Ashton, both Amli's and 360 condos. The hard part would be re-configuring the Lavaca and Guadalupe street entrance ramps to be useful AND pedestrian friendly. But if anyone can tackle that project HEB seems like a great candidate.
Hobby Building revitalization gets my vote.