Those new to cycling are often surprised by the impact an apparently small change in, for instance, saddle height can have on ride efficiency and comfort particularly over a longish ride.
Here follows a beginners guide to setting up a road bike, although much of this is also applicable to an MTB:
Firstly set your saddle to roughly the middle of its fore-aft adjustment and set the top "spirit level flat". Female riders can get away with a very slight upwards tilt but blokes need it to be absolutely flat. This is usually achieved by loosening the allen bolt under the saddle, jiggling the saddle around then re-tightening the bolt; it needs to be fairly tight as there are some significant forces at play out on the road.
Next set the saddle height. There will be a clamping bolt in the lug or collar where the seat-pin enters the frame. As a first approximation the saddle height should be set so that, when you're seated on the saddle with the pedal at the bottom, you can rest your heel on the pedal with your knee straight. Thus, in normal pedalling with the ball of you foot on the pedal your knee will be slightly bent. With experience you may find your preferred position is a few mm higher or lower than this, but this approximation is a good place to start.
Now, back to the fore-aft adjustment of the saddle; this is the trickiest to explain. The importance of getting this right is to get your knee in the correct position relative to the pedal axel during the downward power stroke. If your saddle is too far back relative to the pedal axel then your knee will be too far back and the joint too extended putting unnecessary strain on your knee ligaments. Cyclists, mercifully, do not generally suffer from too many injuries (unless we fall off) but this is one area that can cause trouble. If you have small feet then push your saddle well forward, this will ease the strain on your knees. This is particularly the case if you have an old frame with a relaxed seat tube angle (one that slopes back a long way).
The next job is to get the handlebars in the right place. Most road riders will set the tops of their bars maybe a couple of cm below the saddle height. If you have long arms then the bars can go lower. Positions like this may be a little uncomfortable when you first start until you get used to it and a good starting point maybe to put the bars level with the saddle. The adjustment is achieved by and large in one of two ways. Traditional quill stems have an allen bolt in the top actuating a clamping device down inside the head tube. Loosen the bolt and give it a tap with a small hammer to release the clamp, slide the quill up or down in the head tube then retighten the bolt. The newer "A-head" systems have clamping bolts on the side. Loosen these. The stem can then be moved up or down on the steerer swapping the spacers above and below. There are a couple of other rules of thumb to get the fore-aft adjustment set correctly. Put your elbow against the nose of the saddle and you fingers on top of the stem; your middle fingertip should be 2-3 cm behind the front edge of your handlebars. Alternatively ride the bike with your hands in the drops; you shouldn't be able to see your front hub - it should be obscured by the handlebars. Unfortunately the fore-aft adjustment is achieved by spending money on either a shorter or longer stem, so make sure you've got everything else right first.
To fine tune the above you should get out on a clubrun and ask your clubmates what they think of your position, they will be able to advise then on further small changes.
The above will give you an efficient riding position and protect your tendons and joints from unnecessary punishment. You will of course still be a little sore on your first long ride as your body is really not used to it. Indeed there is more that can be said about general comfort:
There are five pressure points; two hands, two feet and a bum on the saddle. Relief can be achieved by spreading the load appropriately between these points. You will see many novice riders on "sit-up and beg" bikes pedalling serenely through the countryside. This looks comfortable but all the pressure is on the saddle and it's only a matter of time.. Lowering the bars shifts some weight to the hands. Pedalling a bit harder shifts some weight to the feet.
Wear mitts
Wear cycling shorts with a chamois (nothing underneath)
Don't overtighten shoes or toe-straps
(See the Jargon page for an explanation of any terms you are unfamiliar with)