RuneISA is used in 'Unknown Runes' and 'A Legacy of Darkness', the others are unrelated to ISA.

If you want the most up-to-date version of the ISA spec/VM check here in RuneISA folder. The version in Unknown Runes is missing some bug fixes, debug functionality, SYSCALL extensions, etc., while the version in DarkLegacy is also missing most of the same except it has the SYSCALL extensions.

If you want to know how I made it, you can check it out here

Then there is 'The Lich's Token', which uses a custom protocol whose spec you can find here.