I really wanted to make this a longer, more comprehnsive post, but I don't have time anymore.
Anyway, while the suburban malls and internet retail are doing no favors for downtown crossing, I don't think that's what's kill(ed/ing) it.
1) Newbury Street. Your standard department stores (filenes, macys, sears) have been continually going downmarket for a few deades. Newbury street has filled this void, and also grabbed middle class shoppers as you go closer to the mass ave side. There are also some bigger spaces that can compete with the floorplates in DTX. There is also the shop/eat and shop/be seen dynamic that has not been prolific in downtown for a while. When DTX was thriving it didn't have to compete with this retail beast on the other side of the common.
2) The pru/copley place. If Newbury Street wasn't enough to syphon off customers, this was. Hell, it was branded as "the new boston". It was literally designed to replace the center city, which it did. It has massive modern floorplates for department stores and is indoors and climate controlled. It has also lead to a retail powerhouse developing on Boylston, and of course is near Newbury. Again, DTX didn't have to compete with this, it was a rail yard and a dingy strip of dirty buildings back in the day.
3) Supermarkets. Not directly hitting DTX here, but supermarkets replaced storefronts in all the neighborhoods formerly occupied with butchers, cheese shops, bakeries, dry goods stores, etc. All these vacant store fronts (where they didn't remain vacant) were replaced with smaller stores that keep people from going downtown to shop in the first place. Payless, radio shack, etc can all fit in these spaces.
4) Entertainment district. One of the great things about how downtown used to work was going to see a show and shopping all at once. Today the theatres are a fraction of what they are, and theatres are also not exactly super popular anyway. There are clubs, but they have a demographic and are incresingly dangerous. One of the reasons times square works so well is not just ZOMG FLASHING LIGHTS AND TELEVISION (although boston needs way more of this) but that its ajacent to 42nd street. More, bigger clubs with both live music and dancing would help alot. Especially daytime shows that would draw a different crowd.
5) City centers naturally shift and realign with time. Boston has spent too much time trying to perserve a retail district that has been trying to die. If the trend to mixed use had started decades ago we wouldn't even be having this conversation