There are numerous possibilities outside Skype.
First; the iPad fully supports the three ring headset that Apple sells. Both the stock Apple Earphones that ship with every iPhone, and even the Apple In-Ear Headphones. Meaning that you can use third ring microphone for any/all input methods. And, of course, all iPads have built-in speakers and microphones, so you can even use it in a "Speaker Phone" style of use.
If you have access to a Asterisk or similar SIP PBX server, then you have access to a myriad of Softphone applications, many of which are very capable and support all the latest features (namely backgrounding) including 3G calling where applicable. Take a gander at AppShopper.com's list of results when searching for "softphone".
While not an official recommendation because I haven't used it personally, I do give a nod to Counterpath's Bria app, because I've used Counterpath's SIP clients on the desktop for years.