Wordpress has come a long way since the days of WPMU. In the event you're not aware, multisite functionality has been built into the wordpress core since 3.0; and it's a far cry better now than it was when it was wpmu.
I'd say that if you're dead set on using just the one domain, then go the multisite route using subdomains. And hell, if you plan on starting new sites under different domains.. you can add them into the same multisite installation as well by using the domain mapping plugin.
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