The fact that everyone uses his premature optimization is the root of evil remark is hilarious to me. The level of optimization in Knuths writing makes it evident that upfront efficiency effort is worthwhile. Just don't overdo it.
But don't trust me on that quote. Just open book 3 (chapter 5 and 6, sorting and searching) and go read the tape drive simulations of merge sort yourself. You can't miss the printouts, they're huge.