What can't you do in Excel?
mattmcknight: I think something that mixes structured and tabular data together would be great. If you had a worksheet style 
"dynamically typed" structure that was supplemented by some structured tables of data that could be easily referenced and updated by Excel style formulas, it would be very useful.  In this way the spreadsheet sits as a layer on top of several database tables that can be shared between users. I sort of imagine the ultra-flexible spreadsheet on one monitor and this floating collection of data tables on the other one. It's a hybrid.