--prefix= exists to configure the install location, and you shouldn't use any other mechanism for that.
DESTDIR exists to add another prefix on top of what --prefix= specifies, for the purpose of temporarily copying the program into, for example for packaging. A lot of programs will not run from their DESTDIR location, and they must be copied out of DESTDIR to run.
For example, --prefix=/foo DESTDIR=/bar will install into /bar/foo, but running /bar/foo/bin/prog will not function properly, until you "mv /bar/foo /foo" and run it as /foo/bin/prog. There's a very limited set of programs that will try to figure out their prefix at runtime, by checking the location of the binary, but this is hard to do properly and comes with caveats, and the programs that support this are few and far between.
DESTDIR exists to add another prefix on top of what --prefix= specifies, for the purpose of temporarily copying the program into, for example for packaging. A lot of programs will not run from their DESTDIR location, and they must be copied out of DESTDIR to run.
For example, --prefix=/foo DESTDIR=/bar will install into /bar/foo, but running /bar/foo/bin/prog will not function properly, until you "mv /bar/foo /foo" and run it as /foo/bin/prog. There's a very limited set of programs that will try to figure out their prefix at runtime, by checking the location of the binary, but this is hard to do properly and comes with caveats, and the programs that support this are few and far between.