Some of us have used the services of PCB houses that offer low-volume packages suitable for prototyping. For example I've had good results from
ExpressPCB, and I'm sure there are other good suppliers out there. But sometimes the package deal comes with a limit on the number of holes, and that can constrain your design.
In case anyone finds the technique useful, here's a photo showing a project on which I was able to stretch the hole budget by manually drilling. In this case it allowed me to include some PLCC sockets which otherwise would have been been unaffordable, hole-wise.
The easiest way to add holes is with a hand-held electric drill. (Sometimes as a drilling template I use a scrap of pre-drilled proto-board material.) Hand-held drilling is adequate only for very simple cases.
The board in the photo was drilled on a vertical milling machine, with handwheels used to control X-Y position of the table. That worked out very conveniently, since one revolution of a handwheel would result in .1" of travel.

Even so, it was imperative to use a center punch first, or else the tiny drill would "walk" off the slightly convex solder pads. IOW I had to begin by using X-Y positioning to center-punch every location to be drilled. After the dimples from the punch were precisely located, I found it was easy to do the actual drilling simply by hand-locating the PCB under the drill bit; the bit is flexible enough find the dimple despite any minor misalignment.
Obviously manual drilling is for low-volume and prototypes only. And of course there's no plate-through when you drill the hole yourself.
Jeff
http://LaughtonElectronics.com