To satisfy my curiosity I wrote the backtracking control version you mentioned and I was surprised how simple it is:

while (<DATA>) {
  print;
  s[ ^ (START) ( | \s.*? ) (END) (*COMMIT) $ ]
   [ $1 . $2 . 'insert' . $3 ]ex;
  print;
}

__DATA__
STARTEND
STARTENDEND
START SOMETHING END
STARTSOMETHINGEND
START  END
START ENDEND
STARTSTARTENDEND
STARTSTART ENDEND
[download]

For comparison here's the other form:

  s[ ^ (START) ( | \s (?:(?!END).)* ) (END) $ ]
   [ $1 . $2 . 'insert' . $3 ]ex;
[download]