And unfortunately, for a lot of modern algorithms, you're going to have dive into SIMD-like algorithms, something MMIX doesn't have. Also, a lot of modern processors have a decent suite of bitwise operations (e.g., count leading/trailing zeros/ones, popcount) that is also missing from MMIX.
The programming languages that are in favor may change from decade to decade, but so to does most of the assembly language techniques.
Don's first computer was the IBM 650 https://en.wikipedia.org/wiki/IBM_650?useskin=vector see also http://ed-thelen.org/comp-hist/KnuthIBM650Appreciation.pdf so MIX was a simplified version of the 650 because, well, it's well-defined and simple -- and Don knew a popular IBM machine very well. And there's this, in Vol 1:
This series of books is affectionately dedicated to the Type 650 computer once installed at Case Institute of Technology, in remembrance of many pleasant evenings.
MMIX is for all you youngsters who think RISC is all the rage ;-) and I think he does an admirable job creating a fully-defined machine that does use more modern hardware techniques. The fact that he fully defines his underlying machine is exactly correct, because it lays the foundation for precisely expressing the algorithms, and for giving Time and Space (runtime) estimates.
I believe it's fundamentally incorrect to think of these abstract machines as 'assembly language' but rather, I think, they define a stable foundation onto which accurately described algorithms can be expressed. You're supposed to 'play computer' and follow along -- step by step -- to understand the deep details of the algorithms.
(There's another criticism to level at pseudo-assembly language, which is that modern high-performance processors are superscalar with cache hierarchies, which makes the analysis of execution time itself difficult from the kind of first principles that Knuth is working at. I can appreciate why Knuth is working differently from the more traditional big-O notation of typical algorithms classes, but it does need to be acknowledged that it does sap the treatise of its supposedly timeless quality.)
I think, tho, the fundamental reason is: he specs the machine. It does exactly what he says it does. No edge cases, no surprising behavior that LLVM IR or WASM might have; also, I'm sure he spec'd it to make the algorithms he implements elegant or at least more understandable.
I suspect part our views comes from the purity of Mathematics (Knuth) and the actuality of Computer Science. I'm even sympathetic to your view, because then we could verbatim copy Knuth's algos to WASM etc and run them, and we get a twofer: a deeper understanding of the algo AND a deeper understanding of the underlying V-ISA (PTX, BEAM, WASM, LLVM IR, etc).
I think the learning / understanding of the algos Knuth presents partially comes from us Playing Computer, and manually going through the code. It's that pedagogy comes first, I think.
Next time I run into Don, I'll ask him about this. 'cause you're also correct about L1...Ln caches affecting performance drastically.
(And, yes, I had wondered why Don did MMIX he didn't create a "RISC-V" before there was a RISC-V; that is, why didn't he create the Next Great RISC Machine? He said he talked with John Hennessy and Richard Sites. This was in 1990.)
Here's HN on RISC-V vs MMIX: https://news.ycombinator.com/item?id=14635361
They were all the rage for a while, because they make procedure calls fast but turn out to have subtle issues in highly-multithreaded scenarios.