The basic idea is that \paper{...} should contain
settings that relate to the paper layout of the full
document. Similarly \layout{...} should contain settings
for score layout, which could be changed from score to
score within the same document. For example, leftmargin
is a typical paper variable whereas betweensystemspace
is a typical layout variable.
As far as I know, a \layout{...} block can be placed either
on the top level or within a \score{...}. In the former case,
it applies to all subsequent \score{...} blocks whereas it
only applies to the current score in the latter case.
As an exception, I think that if you only have one \layout{...}
section on the top level, then it applies to all \score sections,
not only to those that appear later in the file.
So, something like
\score {
\STUFF
}%end score
\score {
\STUFF
\layout{betweensystemspace = 2.50\in}
}%end score
should probably work.