For security purposes a total isolation of applications may be required. Meaning no single line of code, nor any resource shoul dbe shared. In this case you need to have separate instances. As well, when one eZ Publish instance hosts say 2 applications, which have different evolution paces, the tie-in of the 2 applications being on the same instance may reduce flexibility and prevent from having 2 very different evolution/maintenance paces.
I think we should enhance the initial thread with these considerations, should bring up useful points: http://share.ez.no/forums/setup-d.../multiple-siteaccess-design-solution
My 2 cents, cheers,
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Nicolas Pastorino
Director Community - eZ
Member of the Community Project Board