I'm using R for largish datasets. When compiled on a 64-bit linux, it can address plenty of memory. The windows version is limited to 1.5 Gb, even in 64-bit windows. This is bound to change as Revolution computing have a 64-bit windows R that works (and adds some Parallel libraries). But that is not free, and it's still in beta. We are getting one. I think 64-bit R + resolver one (no limits for spreadsheet size) can get a lot done in a very visual way. I just happen to catch bugs faster when I color-code cells, but this is impossible to do in straight R (fix() and edit() suck!) or in excel because of spreadsheet limits. The combo I propose (don't have it yet) will be expensive but worth it I think.