- Estimated achievement difficulty: 6/10
- Offline: 50 
- Online: 0 
- Estimated time for 1000: 30+ hours.
- Minimum playthroughs: 3-4 [4-5 recommended]
- Missable achievements: The photo achievements are easy to miss if you forget 1 or 2 you're probably doomed
- Glitched achievements: None
First of no matter how you go about it this is a long game to get all achievements. On top of that the save system is a bit awkward (you can only save in specific places not just anywhere), but once used to it you'll be fine.
I'll just go through the minimum number of playthrough although I recommend doing at least 1 playthrough to get acquainted with the game (on this first playthrough you'll also get some of the achievements regardless of whether or not you're going for them).
And maybe split up playthrough 2 into 2 seperate playthroughs as well (doing the "Saint" and "Transmissionary" achievements at the same time could be tricky.
Achievements: "Zombie Hunter", "Zombie Killer", "Zombie Genocider", "Gourmet", "PP Collector", "Sharp Dresser", "Clothes Horse"
This playthrough will seem to make the rest of the game go easier. You'll ignore the story and go for some of the achievements that unlock extra items in the game. Most notably the Real Mega Buster which is the most powerful firearm (pun intended ) in the game.
For the "Zombie Genocider" Achievement you can find a video of a great route over here.
For the others see the achievement guide below.
Achievements: "Self Defense", "Peace Keeper", "Punisher", "Legendary Soldier", "Tour Guide", "Full Set", "Humanist", "Life Saver", "Saint", "Portraiture", "Census Taker", "Psycho Photo", "Psycho Collector", "Snuff Shot B", "Snuff Shot J", "Transmissionary", "Overtime Mode", "Infinity Mode", "3 Day Survivor"
This playthrough you'll focus on the story and saving/photographing a lot of people.
Now for this playthrough be sure to have guides for "Saint" and "Transmissionary" with you and read them through before going for this it will save you a lot off frustration.
The achievement guide as links for both, although I preferred to use this one for "Saint".
For the survivor photograph achievements (all 3 of them) I just waited until I saved everybody and then photograph them in the security room (I did it after case 6-1). You should also photograph everybody at the beginning of the game (when there are no zombies yet). These people can't be saved but will count for the photo achievements.
The psychopaths you'll need to photograph when you encounter them (alive or dead doesn't matter).
Achievements: "5 Day Survivor", "7 Day Survivor"
This is not really a playthrough as it has to be done in a separate mode which you unlock during playthrough 2 (mode = infinity mode).
For these 2 you'll need a whole lot of time since you can't save at all and 1 day in-game is about 2 real life hours. So you'll need 16 hours at least(counted 2h for load screens and breaks).
Be sure to have a map and read up on all you can find before attempting this. I won't list everything here as there are numerous topics in the forum about this.
Achievements: All the achievements you haven't got yet
You'll get some of the remainder of the achievements while doing the other playthroughs. For the ones you don't you can start a new game which you'll only need to complete partially (unless you want the unlockables, more on that later).
The ones you probably won't get during the other playthroughs are: "Frank the Pimp", "Strike!", "Hella Copter", "Perfect Gunner", "Indoorsman", "Outdoorsman".
For "Frank the pimp" there is a nice video guide over
Like mentioned before there are a couple of unlockables. To get the unlockables you have to complete your game first. What I mean by this is that you have to get an ending.
The fastest ending is "Ending F" which you get for not getting all the bomb in case 7-2, but you'll have to be doing all cases to get there so it might be a pain to do.
You can also ignore all cases and show up at the heliport at noon on day 3 to get an ending which leaves you with a lot of time to spend on other achievements you haven't got.
You'll find the unlockables in the securty room left of the air vent the next time you start a game.
Here is a list of the achievements and their unlockables:
Perfect Gunner: Ammo Belt
5 Day Survivor: Laser Sword
7 Day Survivor: Arthur's Boxers
Saint: Cop Hat
PP Collector: Hockey Mask
Transmissionary: Mall Employee Uniform
Unbreakable: Mega Man Boots
Punisher: Mega Man Tights
Carjacker: Prisoner Garb
Item Smasher: Pro Wrestling Boots
Karate Champ: Pro Wrestling Briefs
Zombie Genocide: Real Mega Buster
Legendary Soldier: Special Forces Boots
Hella Copter: Special Forces Uniform
Census Taker: White Hat