My biggest points are lower muscle mass because of the lower g (gravity) in an artificial habitat and fragile, less dense bones. They would also get sunburns quicker, because most of the time they are being covered from regular sunlight by gigantic shields, thus relying on supplemented vitamine D. These humans would be physically handicapped in an Earth like planet setting, although more trained, because they'd have a strict training rigour to keep themselves relatively healthy.
Is this idea justified by what we already know about space? Is there a way to make it more realistic? What other side effects can you think of? And please give me links to all of the sources you're using.