I am looking to change from v0.243 to v0.221. Is there a way to do that without having to re-install the whole thing?

Not really, but "the whole thing" isn't more than a handful of files. Keep backups of enblocal.ini and enbseries.ini if you have settings you want to copy over.

So, exactly which files to I need to replace?

There's quite a gap between them, so you should probably replace almost everything, but everything is basically the enbseries folder, the d3d9.dll, enbhost.exe, the .fx files and enblocal.ini and enbseries.ini (as there have been several changes in them). I keep backups of my enb series with the changes I've made to the ini-files, so it takes just a couple of seconds to switch - and of course a minute or so to copy over ini settings to a new release.

BTW, not my business, but why do you want to switch back to 221? There have been several rather awesome changes to water and clouds/sky since then IMO.