I love Excel and it's one program that's always open on my computer. But the thing that still kills me after all these years is that every open Excel process shares the same undo stack.
Say you have have Excel Process A and Process B, and you make an edit in A, then an edit in B, then an edit in A again. If you try to undo the edit in B, it will instead undo the edit you did in A. Infuriating.