Having multiple blogs in a custom domain is a simple matter - but like all custom domain details, it's rigid in its simplicity.
A custom domain array consists of a home blog, plus any number of alternate blogs. These alternate blogs are generally setup as virtual hosts, using "CNAME" referrals to "ghs.google.com".
A single domain can include any number of virtual hosts, in an array.
If you want to organise your virtual hosts in separate groups, each group administered by a different individual or organisation, you setup subdomains. Each subdomain can be hosted on the same or different DNS server(s) as the main domain, and can be administered separately, with no interference between the subdomains.
Adding virtual hosts to your domain is simple - one more virtual host is simply one (or possibly, two) more "CNAME" to "ghs.google.com". Adding subdomains to your domain, on the other hand, is a bit more work - and should be done only if you're comfortable with DNS administration. Make it easy on yourself - stick to setting up virtual hosts, and leave the task of setting up the subdomains to those with complex administrative structures, like enterprise complex organisations.
For more insight about subdomains and virtual hosts, see