If you're riding in cycling shoes, it's important that the cleats on the soles are positioned correctly. There are two important adjustments, fore/aft and angular. The former is easy to find, the latter takes some careful trial and error.
The cleat should be positioned so that the balls of your feet rest over the centers of the pedals (the axles) when you're pedaling (photo A). Sight from the top when you're on the bike to check this (hold your feet level). The balls of your feet form protrusions on the insides of the shoes and these should rest right over the axles. If not, adjust the cleats as needed.
Ideally, your cleat position allows resting your feet in a natural position on the pedals. Otherwise, you could injure your knees. Usually, aligning the cleats with an imaginary line that bisects the soles provides a safe starting position (photo B). But, go for some very easy rides to check the position and ensure it's right for your knees. If you feel any stress or strain, change the angle slightly to eliminate discomfort.
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When you've found an ideal cleat position, trace lines around the cleats so you can easily replace a worn cleat and reposition a loose one.
Use quality tools and work with care so you don't strip the cleat bolts. Also, check your hardware to make sure it’s still tight after about 5 hours of riding.
If you're using toe clips and straps, make sure the clips hold your feet in the optimum position (balls of the feet over the centers of the pedals). If not, get different-size clips. If you've got huge feet, place spacers between the clips and pedals to "lengthen" the clips.