Well, even as-is, it turns out that the kind of assembly language that Knuth originally wrote it in itself had a very short lifespan. MIX assumes a single accumulator register for arithmetic, which hasn't been a common processor architecture since around the 1980s. MMIX is redesigned to be more RISC, but it also uses a dynamic register window concept (which itself I think was only used on Itanium, and we all know how that architecture went down).

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.

Sparc and Xtensa also have register windows, although each has a slightly different implementation.

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.