Utilizing defense up effectively means understanding its uses and limitations so that your playstyle can reflect the benefits.
If you tend to carelessly push toward opponents or get caught off guard then defense up will never save you in those situations.
I'll try to break down the benefits and how to utilize them to your advantage along with required minimum defense.
1. Counter burst bomb + 1 shot. Most weapons that use this technique only stack enough damage for it to work with no defense. With only one defense sub you'll force your opponent to land an extra hit on you and since it's so easy to counter all defense builds gain this benefit.
2. Counter quick shot charger. If you can make a charger miss their fully charged shot then advance on their position you can often take them out before they retreat if you have range. Minimum 9 defense subs, preferred is more than 1 main 9 subs.
3. Increasing number of indirect blaster shots. If you can position yourself where you can't be hit directly and you'll be hit by the farthest reaches of blast radius you should be able to escape while running and reposition to take them out. Minimum 9 subs, recommended more than 1 main 9 subs.
4. Brushes and rollers. If you maneuver to the side of shots you can generally take an extra hit while being able to take them out. Minimum 9 subs, recommended 1 main 9 subs.
5. Tentatek and .52 gal. It is preferable to play outside or at the edge of their range to make the extra hit you can absorb matter. Running in will still get you killed. Minimum 1 main 7 subs, recommended 2 main 9 subs
6. In general your chances of surviving a retreat are better so know when to back off and always be sure to dip into your ink for a quick recovery after being hit as you won't survive as easily if you keep some damage on you.
On top of all this running ink resistance with a defense build is incredibly important as it decreases damage taken from being in enemy ink while also letting faster maneuverability in case you swim over enemy puddles.
In most benefits range is a must so defense builds benefit mid-long range weapons the most. Ex: .96 gal Deco
Personally I run 2 main 9 defense and ink resistance while playing either the .96 Gal Deco or Slosher Deco so I'm pretty familiar with the benefits.