The first part (locating the hardware or low-level configuring) is assigning each port an IO address, IRQ, and name (such as ttyS2). This IO-IRQ pair must be set in both the hardware and told to the serial driver. We might just call this "io-irq" configuring for short. The "setserial" program is sometimes used to tell the driver. PnP methods, jumpers, etc, are used to set the hardware. Details will be supplied later. If you need to configure but don't understand certain details it's easy to get into trouble. See Locating the Serial Port: IO address IRQs What is Setserial
The second part (high-level configuring) is assigning it a speed (such as 115.2k bits/sec), selecting flow control, etc. This is often done by communication programs such as PPP, minicom, or by getty (which you may run on the port so that others may log into your computer). However you will need to tell these programs what speed you want, etc. by using a menu or a configuration file. This high-level configuring may also be done with the stty program. stty is also useful to view the current status if you're having problems. See the section Stty