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I would agree only do hosted solutuons for things you don't mind replacing when the service provider goes out of business / raises prices / starts to suck / no longer meets your needs.
OScommerce is probably the most popular cart and there are a ton of plugins for it. All of those customizations are probably already done, you just install the plugins you want. It's kind of spaghetti code, though.
Zen Cart might be a reasonable choice too.
Then you have special purpose carts, like outre system for selling content. It's definitely a lot better for that specific tyoe of store than any generic cart system.
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