'lean' operating system/software usage setup small enough to fit /run entirely in ram (and/or 100MB+ cpu lvl 1 cache) would avoid i/o issues. --power backup not optional.
Offtopic but lately I've been building a "new" physical C64 which is nearly done - SD2IEC + Epyx Fastload for fast disc emulation and Kung Fu Flash for near instant .prg loading. Related to the discussion I think KFF is faster to load a .prg than my Windows is loading an .exe - not that I would ever do actual work on a C64 with or without KFF.