What are the best targets to go for in a real life defense situation? My philosophy on this topic is to keep it as simple as possible.When your amped & charged with adrenaline in the grip of the fight or flight response, it becomes very difficult to execute fine motor skills. Even trained people tend to default to gross motor skill movements when their life is on the line.Overly complex techniques requiring a lot of manual dexterity will be hard to pull off.
So, stick to targeting area's of the body that are "anatomically weak"(cannot be strengthed) using functional gross motor skill movements.This doesn't always mean instinctive responses as many times our instincts are wrong although it's ideal to build on built in instinctive responses such as the startle/flinch.In other words, we "educate" our instincts & natural reflexive reactions with proper training.
Anatomical weak areas include the nose/philtrum,the eyes,the temple,side of the jaw,the ear,the throat,the back of the neck/spine/brain stem,the side of the neck, fingers,ankles, shins,throat hollow,collarbone, knee, the joints,groin, the feet, ribs(lower part/floating ribs or right around the serratus area not covered by heavy muscle).
A good general rule is attack hard body parts with a "padded" weapon(like your palm) and attack soft target areas with a hard weapon(like fist). Meaning don't hit the skull with a fist,but rather a open hand.
Also, be careful striking toward the mouth.It's very easy to gouge or even break your own hand on their teeth by striking toward the mouth.That's why the side of the jaw or bottom of the chin are targeted if your hitting the lower part of the face.With the nose, you can come down with a palm heel or hammerfist negating the risk of hitting the teeth although there is nothing wrong with a good straight punch or palm heel either.An arcing punch to the face will give you the downward angle,but if they duck the head down slightly,you may hit the forehead(the hardest part of the skull) and may take your hand out of the fight. Driving up through the philtrum is effective,but with greater risk of hitting the teeth.Using the blade of the forearm in a shearing or backhand motion to strike side of the neck or at a 45 degree is very effective and can result in a knock-out since there are a lot of nerves and blood pressure sensors contained around the carotid arteries.Pick up a copy of Gray's anatomy and study the layout of the Human body, so you understand better what your hitting.
Fingers are easily broken, eyes are an easy target in a grappling situation(if warranted) and ankles can be stomped resulting in immobility lose allowing escape. Any throw, sweep or takedown on the street can result in the attacker hitting his head, so take that into consideration.
The main thing to remember is to keep it simple, functional & be confident in your knowledge and training that you know where & how to hit in a real defense situation.