To get the Godhead first you need to have "The Lost" character unlocked.

To unlock The Lost:

The Lost is unlocked by dying consecutively with certain characters, with no other deaths or exiting the game in between runs.

1-Isaac must die to a Mulliboom in one of the Basement floors. (is the version of Mulligan that got a bomb attach to him)
2-Magdalene must die to her own bomb in one of the Caves floors.
3-Judas must die to Mom in one of the Depths or Necropolis floors. It does not have to be specifically to Mom's foot stomp attack. Dying to the flesh walls/hand grab/blood shot will yield a death screen with the cause of death being Mom's Foot.
4-Azazel must die after beating the Fallen in the Satan boss fight in Sheol. He has to die by projectiles.
(In other words... don't die to Satan's brimstone.)
-Dying to Satan via his stomp does unlock The Lost.

Note: A good strategy is to use seeds, EXCEPT on the last death (the Azazel one) the Azazel's death need to be done on a "normal" run.

In afterbirth to unlock the lost just die in the sacrifice room with the missing poster trinket.

So let's start (REALLY start, the "fun part"):

To get the "Godhead" achievement, you need to beat all hard modes with The Lost (Mom's Heart/It Lives, Boss Rush Room, Sheol, Dark Room, Cathedral & The Chest, except Mega-Satan, thank god, cause he is not a hard boss (in my opnion) but he is hard to defeat without taking a hit.)

First of all just a tip (I did not do what i will recommend now, but that was because I'm stupid) even if you don't got the other things unlocked by playing as The Lost, start playing with him on hard mode, because you gonna be SOOOO pissed off with this character at the end, that will suck have to play the things again with him on hard to get the godhead, and of course it can't be much WORSE than already is, playing with him. So one hit and it's over, but don't panick, there are some tatics, or exploits or whatever you call this, that i learned by myself doing the godhead.

So keep holding the ♥♥♥♥♥♥♥♥ "R" to reset the file until you got something good to start to play, i would recommend something to start a good massive DPS (Damage Per Second) run. But if "Gnawed Leaf" spawns, you can TRY to keep on with it, because if you got something like a combo of: "Gnawed Leaf + Daddy's Love" for example you become immortal, you don't even need to play no longer. Or unicorn stump+mom's knife should do it too, but i never got any luck dropping those "combos", just the items separately.

Anyway... there are two things that you really should know, the things that i said above "tattics, exploits whatever you wan't to call." if you die, but don't appear the screen of the "Isaac's last wish", you know the letter XOXO for Guppy anyway, if you die but you press alt+f4 to exit the game before "Isaac's last wish" appear on the screen, when you back on the game, you would be able to continue your file.

BUT will start the floor again since it's begin, UNLESS you use this another thing that i learned on my last run with The Lost, if you for example finished one "hard" room, and back to the main menu, it will "save", and when you click continue, it will continue since that finished room.

Use those two things together and you're 80% on the way to be golden, the others 20% deppends on the run (on luck).

This "save" thing, can be used on Boss Rush Room too, every time you defeat a pair of bosses, if you back on main menu will save. (Total waves are 15, so i would recommend to do it at least 1 time (i did it before Peep II 'cause he hits me pratically always.)

I would advyse you, to take Dark Room out of your way at first (if you are with a good file), because it's the most difficult. And another thing (besides dark room being the hardest, like i said) The Mind and the Soul items will help you A LOT in getting the other run through Cathedral and The Chest (because The Mind reveals the entire map (including secret rooms) for all floors, unless if you get a "The Lost curse" I think... and The Soul grants 2 soul hearts (that means nothing for The Lost character of course...) *BUT will let your deflect shots and flies so its a really helpful passive.*

Note: I will put an image showing a character deflecting It lives shots, so you can understand more or less what i mean about "The Soul".

NOTE: DO NOT ENTER ANY CURSE ROOM (the rooms with spikes on the floor) because obviously you fly, but you will take a damage when leaving the room, just like the original game. And with those things that i said before sometimes it bug and "save" the run with you inside the curse room. Only enter on a curse room if you got something like: "The Hermit, The Fool, The Stars, Teleport.../or if is adjacent to another room, so you enter through this room (secret room) before to be sure, so you can acess the curse room and exit without going through the spikes (neither entering or exiting the room), through the bombed wall.", by the way i think if you kill yourself for the spikes and quit the game with alt+f4, you will back on the begin of the floor (or the last place that you "saved" BUT i'm not sure.)

NOTE 2: You can enter on the curse room of the first floor of course trying to get a Dead Cat, because this ♥♥♥♥ helps a lot because 1- You don't need to continue closing the game with alt+f4 because this is ♥♥♥♥♥♥' annoying. 2- If you die with one hit, so Dead Cat is a good item, because you will die with one hit one way or another, so its better have 9x lives.

NOTE 3**: (UPDATE): Now is a little easier to finish the game as The Lost because he no longer starts ONLY with flight, but also spectral tears, the D4 (If avaible) and Holy Mantle (DLC and If unlocked).
(**Obs: You had to unlock the D4 first so The Lost can start with it. (same rule as D6 for Isaac)
It's unlocked by destroying 30 slot machines.
And the Holy Mantle is DLC only (Afterbirth), to The Lost start with it, you had to donate 879 coins to the greed machine.**)


Well i think that's it, good luck guys. ^^

They finally made the option to achievements/unlocks remaining enabled even with mods turned ON, without it stop counting the achievements. (as it was before)

Note: Mods no longer disable achievements after beating Mom once.

(I don't know if is only Mom herself, her heart too and/or it lives also...)

I got this information at http://steamproxy.com/steamstore

Anyway... i still didn't use any mod that affects too much the game (New classes, new transformations etc etc) and I will not, until I 100% the achievements. But those mods that i will list below, i really really recommend 'em a lot, for your normal experience from the gameplay or even (essentially) to get your progression over all the characters unlockables:

https://steamproxy.com/sharedfiles/filedetails/?id=836319872&searchtext=
https://steamproxy.com/sharedfiles/filedetails/?id=834317560&searchtext=
Notes: About the first mod: ESSENTIAL! You can finally stop going to alt+tab/shift+tab to search "what is that?" in the wikia of the game all time.
For the second one: You need to enable the option "Found Hud: inside your game options. In order to use this one.

The Lost can use the button to stop the spawn at any time he wants without taking damage, so it's quite bit easy to finish the DLC.

And all the tips i said on the guide (alt + f4, head back to the menu for saving the game... everything still works so...) this thing of The Lost now start with a bunch of items, use the button of greed any time he wants, take sacrifices for free, plus my tips on this guide.

You should finish the greed DLC without much trouble.

If you be lucky, some combos that i mention here will really help you (if you guys know/remember more combos, place on the comments)

Gnawed Leaf + Daddy's Love (You don't even have to play no longer, this combo will able you even to kill Mega Satan while you watch TV LoL)
Gnawed Leaf + Midas Touch/The Virus (Same as Daddy's Love but more decent in my opnion.)
Gnawed Leaf + Mom's Knife
Unicorn Stump + Mom's Knife (Immortality for every room and highly DPS damage, this one is GG E-Z except for Boss Rush, but every other room and boss you will nail 'em.)
Brimstone + Tammy's Head (Massive DPS damage for each room)
Brimstone + Spoon Bender (Brimstone will be redirected for enemies thx to the Spoon Bender)
Brimstone + Spoon Bender + Tammy's Head (GG E-Z that's all i can say)

All The Ludovico combos that i mention here will be basicaly the same rule, the tears will become a large ring (depending on the combo the ring will be more huge, less huge or more strong in damage)
but are basically the same to understand how will work:

The Ludovico Technique + Brimstone
The Ludovico Technique + Brimstone + A Lump Of Coal
The Ludovico Technique + Brimstone + Pulse Worm
The Ludovico Technique + Brimstone + Wiggle Worm
The Ludovico Technique + Brimstone + Proptosis
The Ludovico Technique + Technology
The Ludovico Technique + Technology + Spoon Bender
The Ludovico Technique + Spoon Bender + Brimstone