There's not much reason to define USE_MULTI without USE_ITHREADS. It might be useful for embedding, if you want to manage multiple interpreters, but I wouldn't be too surprised if that broke.

USE_IMP_SYS might also be useful when embedded since it does nearly all file handling via callbacks (see iperlsys.h) which you can override if you want to virtualize access to the filesystem. There's little need for that for non-threaded and non-embedded perl though. This is used to maintain per-pseudo-process environment variables and current directories for pseudo-fork.