Despite the fact, that Delsin, almost from the beginning of the game, has a range of useful and powerful abilities at his disposal, he is not invincible and this fact becomes especially clear while playing on the highest difficulty level. I would recommend planning your skirmishes ahead, especially when you're expecting to be going against a substantial enemy force - as long as the game allows you to prepare for it (frequently the enemy forces appear from thin air and you won't have the time needed to prepare yourself).
Getting onto a roof of a building adjacent to your current goal is generally a good idea, as you can get a glimpse of the area, where you have to go and how well the region is protected. Also, you should establish a "list of priorities" (taking out the observation towers at first, for instance) and try to hold onto it after the fighting begins. Furthermore, you can try to attack the enemies by surprise - Comet Drop or Orbital Drop powers come in handy here. It will allow you to take out part of the enemies before the actual encounter begins, or demolish a barricade or other object, which otherwise could be a burden.
Fights in inFamous: Second Son can take various forms, but common sense would advise to divide them into those performed in close combat and those, in which you try to keep your distance and attack the enemies from afar. Close combat is recommended while fighting enemies which can't deal effectively with this type of combat, for instance the most regular soldiers of D.U.P., equipped with firearms. Your chain should be able to deal with them without much effort - another advantage of using it is that it doesn't use your smoke reservoirs. If you want to launch some stronger, short-ranged attack, like Cinder Blast (hold down the R2), you should also do it while fighting them in close combat.
Ranged combat is recommended, if you don't want to take unnecessary risk and/or if you're fighting with enemy soldiers or machines, that cannot be hurt with direct attacks (because they can block them, for instance). In this case, your main weapon should be the Smoke Shot, unlocked at the beginning of the game, although you shouldn't forget about other powers (unlocked later in the game), highly effective against enemies located further away (for instance, a Cinder Missile, effective against enemy tanks and helicopters).
Note - a very important aspect of both melee and ranged combat, is that you should try to be on the move all the time, which will make you harder to track for your enemies. The benefits of such a fighting style can be seen practically from the first mission in the Seattle. Remaining in motion will allow you to avoid taking damage from enemy's ranged attacks (especially from snipers),as well as grenades and projectiles fired by enemy vehicles.
The environment in the game inFamous: Second Son is destructible to a degree, as Delsin cannot level entire skyscrapers or bigger objects. You shouldn't, however, have any problems with distinguishing the object, that can be destroyed, and, unless you have your smoke reservoir running on fumes, you should always opt for an aggressive approach. Demolishing a certain object can automatically take out a group of nearby enemies, hinder their attacks, or prevent them from reaching you (when a construction crashes on the street, blocking it entirely).