The downside of spreadsheets is they can really slow your model down. Every cell change triggers a full recompute of the 3D model. VarSets offer much faster performance while sacrificing a couple spreadsheet features. So always choose VarSets over spreadsheets if you can.
On the one hand it's clearly suboptimal for any change, even ones that nothing depends on, to trigger a recompute. But also it feels like there's something a bit broken with spreadsheet dependency resolution in the first place. I've never been able to nail down a test case, but models seem to go over a performance cliff at a certain point. Ordinarily I'd put it down to something being unavoidably quadratic, but I've had cases where I'm certain that the same model is radically slower after being reloaded off disk.