Beating the game under 4 hours might seem like a daunting task, but it's pretty feasible even on Hard if you know what you're doing.
Obviously, you probably want to do this on Speedrun mode which will remove all cutscenes, dialog, and tips that could slow you down, while providing a helpful timer. Keep in mind that this will remove your ability to copy your save since you can only have one speedrun save at a time.
Also, I recommend going for the Low % trophy and playing on Normal since hunting down extra items and retrying because of death costs time.
Quick notes:
1) Head left to get the starting weapon, then go to the upper right part of Eribu for the Nova weapon. Fight the first boss, and get the Drill and the Power Node upgrades beyond him. Head down to Absu and collect the health upgrade just by the entrance.
2) In Absu, head to Elsenova for Kilver. You really don't need any other weapons at this point. Go to the boss, jump over him and shoot him from behind. Get the Address Disruptor, and then the Health Node in the next room.
3) Make your way through Zi to Kur. Go up a little ways and head left. Get the High Jump and head back to Zi.
4) Fight the boss in Zi. This isn't too hard once you get the hang of it, but a slight misstep at the beginning can kill you.
Do short hops through the water and use the disruptor to make a one block platform just under the second tail launcher. From here, hold L1 to lock your position, and fire up and to the left. Once you destroy the launcher, you'll be able to hit the head most of the time, and you are completely safe.
After that, get the Lab Coat and the nearby Health Node before going to Kur.
5) Go up through the second large area of Kur for the drone, then back down to near the first checkpoint. Go through the room above the checkpoint for the Disruptor upgrade.
6) Beat the Kur boss. This one is tough so make sure you hit the checkpoint nearby and quit out of the game when you die if you are taking too long. Run through the boss and hit it with the Kilver from behind. Just as the Flamethrower attack ends, start running right. Now shoot Nove bombs under him and jump over his shots. Unfortunately, there's no other trick here, so reflexes and skill are required.
Grab the Grapple when you are done and use that to get the Enhanced Drone Launcher.
7) Head to Ukkin-Na through Indi (the long area). Once in Ukkin-Na, make your way to the hallucination boss fight. After the fight, go right to find the Trench Coat. head to Edin by way of Indi.
8) In Ukkin-Na, go to the Clone room, then to collect the Address Bomb. Head up to the boss fight. This boss tends to be tough, unless you know the trick.
Move left a little ways so you can step up a level. The Boss will spit at you three times, then lay back to release a swarm at you. Hit them with the Disruptor. The goal is to make them glitch on the higher platform. With them glitched, back up a little to lure the boss on to the area with the glitched swarm. Now you want to destroy the glitched swarm when they overlap with the boss' mouth. If the explosion when they are killed hits the boss in the mouth when the mouth is open, it should instantly kill the boss. The fight can be done in less than a minute.
9) After the fight, get the Drone Teleport and head back down. Get the Health Node on the way. Make your way back to Kur and go to the highest point. Use the Drone Teleport to get you in to the temple E-Kur-Mah.
10) Head up for the Sudran key. Go back, then down to the bottom for the Red Coat.
11) Collect whatever items you want as you have free reign of the map at this point. Keep in mind to leave some time for the final section of the game (40 minutes should be more than enough but you know your skills best) and remember not to go over 38% if you want the low % trophy.
Once you are set, head for Mar-Uru by way of Ukkin-Na.
12) Start climbing and fight the first boss, Sentinel. When the head is exposed and shooting lasers, stand to the left of the beam. From here, start teleporting straight up into the head while shooting the Kilver for massive damage. During off phases when he releases the swarms, head for the corner to the left and keep teleporting into the wall. This will mitigate damage quite a bit. Repeat this process until it is dead.
13) Keep heading up. At the next boss, you can walk right past and into the next room, so do that. Keep climbing and taking checkpoints. Make sure to hit the checkpoint just before the bunch of horizontal laser walls blocking your climb.
14) Make the final ascent to the last boss. Once the battle starts, wait a moment and shoot an Address Bomb to glitch the drones. Now, climb up to the ceiling and use the grapple + teleports to get into the upper right corner. There's an invisible platform here. If you can get on it, even if the drones hit you a couple of times, they'll leave and go under you making you completely safe from harm. At his point, just shoot left to destroy the box. Do this a few times and you're done.
If the trophies don't unlock right away, don't worry. Most of the trophies actually unlock at the final Game Stats screen.