In Gnumeric and OpenOffice.org Calc I am often dealing with uncertain numbers (for example experimental results), but currently there is no way to tie these uncertainties to the numbers, requiring that everything be entered and calculated twice.
Uncertainties in numbers are recognised in graphs (error bars), I think they should be available to any quantity in the application.
It would also be useful if the application could take its own inaccuracies into account by using uncertainties, for example rounding errors could be added on to existing uncertainties.
This would be a killer feature for a spreadsheet for me and many people I know, since that is all I use them for.