Unfortunately apt-cacher-ng's documentation is a bit inaccessible. Aside from not being available on the project's website (it's in PDF form in the documentation directory after you install it), the documentation, although complete, is kind of impenetrable. There also really isn't anything that I could find along the lines of HOW-TOs or FAQs on the 'tubes. I eventually got it worked out, and, at least for the common case, it turned out to be more straight-forward than the documentation leads you to believe. Here's how I set mine up.
I put entries in my acng.conf like the following:
Remap-ubuntu: http://us.archive.ubuntu.com/ubuntu
Remap-medibuntu: http://packages.medibuntu.org/
The way this works is you specify names for each Remap-[whatever] where [whatever] is whatever you want to call it--they just have to be unique. Then the part after the ':' is the literal URL of the repository you're caching including the directory path on that server, if there is one.
The documentation describes a third part that follows a ";". If your second part is the actual URL of the repository, you don't need the third part, as you see above.
In my sources.list, I put
deb http://my-server-name:3142/packages.medibuntu.org hardy free non-free
deb http://my-server-name:3142/us.archive.ubuntu.com/ubuntu hardy main restricted universe multiverse
Here, the URL to the apt repositories is your local server name (port is 3142 unless you change it in acng.conf) followed by a directory that is the exact same as whatever the fully qualified domain name of the real apt repository was, followed by the actual directory path that you appended to the actual apt repository in your acng.conf.
There are lots of other options described in the apt-cacher-ng documentation, but I believe this is the common case, and it's working fine so far.
Update:
The directory structure that gets created under /var/cache looks like:
apt-cacher-ng
|-- canonical-partner
| `-- dists
| `-- hardy
|-- ubuntu
| |-- dists
| | |-- hardy
| | |-- hardy-backports
| | `-- hardy-updates
| `-- pool
| |-- main
| |-- restricted
| `-- universe
`-- ubuntu-security
|-- dists
| `-- hardy-security
`-- pool
|-- main
|-- multiverse
`-- universe