I started off with a multi game with four self-created characters and have included the various NPCs one or two at a time. But like Father Bronze says I discovered I missed out on a lot of the NPC interaction, even though I still ended up doing most of the side quests. At the same time tho' it's really neat to have more than 1 self generated character to develop, particularly if they're classes you can't find among the NPCs.
So I guess on balance I'd still recommend starting with a multi, because its the most flexible, you can balance the number of self + NPCs to your taste and can adjust that balance throughout the game as you meet new NPCs or want to import new characters.
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