"Death: Before there was light, before there was God and the archangels there wasn't nothing, there was the Darkness. A horribly destructive amoral force that was beaten back by God and his archangels in a terrible war. God locked the Darkness away where it could do no harm, and he created a Mark that would serve as both lock and key, which he entrusted to his most valued lieutenant -- Lucifer. But the Mark began to assert its own will, revealed itself as a curse and began to corrupt. Lucifer became jealous of man, God banished Lucifer to Hell, Lucifer passed the Mark to Cain, who passed the Mark to you -- the proverbial finger in the dyke." - Superwiki
It seems like there might be a few issues here plotwise. Maybe we can discuss all the potential issues and come up with solutions for them, and if we can make the entire thing hang together we can collect them and send them to the SPN writers as a mini-Bible (no pun intended).
Questions include (I have also rounded up some of these from various discussions on the main site):
Why does the mark need to be both a lock and a key? Seems somewhat self defeating that. (also a finger in a dike is neither a lock nor a key ... but anyway ...)(also can we spell it 'dike' instead please? Since 'dyke' has other meanings whereas 'dams' can be spelled either way).
How comes god is creating curses? What is wrong with him?
Does Death mean that the darkness was seeping through and corrupting Lucifer? What does amoral mean in this context? Why should something amoral cause a curse? Something immoral might. "Amoral" means not involving questions of right or wrong; without moral quality; neither moral nor immoral. having no moral standards, restraints, or principles; unaware of or indifferent to questions of right or wrong.
Does Lucifer still have part of the mark?
If not the does that mean that the damage caused by having the mark is irreparable?
If Lucifer does have the mark does being in the hell box negate the MOC abilities?
In that case where was Death going to put Dean so that the mark could be still active?
Could Cain have given the mark away entirely thus saving himself from having to be killed?
If so then why didn't he do that instead of sharing it?
Why didn't God remove the mark to someone else? Was it safest on Lucifer?
Did Cain not know the story behind the mark?
What was 'The Mark of Cain' called before Cain got it?
Was Dean under the influence of the mark all season? Which bits were Dean and which bits were MOC Dean?
What does the mark actually do to you? (apart from making you unable to say the words 'I'm sorry' unless you are talking to your car)
Is becoming a demon always going to happen when someone with the mark dies?
Are demons formed from angels the same type of creature as demons formed from humans? Can other types of beings become demons?
Was the first blade really necessary to the action of the mark?
What was the blade's part in all this?
Where did Cas hide the blade?
Didn't Dean ask Cas to kill him because Sam wouldn't? (I feel like he did but I can't find the episode) If Cas's job was to kill Dean if the mark took over why has his failure to do that not been mentioned? Isn't this not 'stopping thinking about yourself for one damn minute' too? Shouldn't Dean be berating him about this? (I haven't seen 10:21 or 10:22 so it is possible he did)
Didn't that conversation include the idea of sending Dean into space also?
Why is everyone comfortable with the idea that 'the mark wasn't affecting Dean so badly, he is always like that'? This is normal Dean? We like this person?
Why is the show suddenly thinking about Dean and space in the same sentence a lot? Why is Tumblr so fascinated by the subject? Why is space and Dean suddenly a thing?
Was it Dean or the mark or both that tried to kill Sam in 10.03?
Why did Dean only kill/try to kill REALLY BAD PEOPLE (and Sam)? Is it because nowadays trying to kill Sam isn't actually a mark against the good guys (which apparently Cole is one of *eyeroll*) in the show's grand scheme of things? Is it because Sam will never hold it against Dean that Dean had several goes at trying to kill him so we can pretend it didn't happen? If so why does the writing of this show suck this badly all of a sudden?
Was it Dean or the mark who missed Sam with the scythe? Did Dean actually intend to go through with killing Sam (I think he did) or did the mark stop him? If he didn't intend to kill him what was the 'forgive me' for?
Boy howdy did Dean get over nearly killing Sam quickly, like, instantaneously! Does that mean his human instincts are damaged by the mark? Does it mean he never intended to kill him? Is this just the brothers being nonchalant? What? How do you spell nonchalant? At some point does Sam get to give Dean a black eye for some or all of what Sam has been put through in the past season and a half since the MOC was entirely not his fault?
Since scythes are notoriously difficult to handle by amateurs (no offense Jensen

Do we know for a fact that a person with the mark cannot kill themselves with the first blade?
Does the DARKNESS!!! have to be spelled in all caps with 3 exclamation marks?
What is the actual order of events WRT the history of the mark? Darkness. Creation. Angels. Mark. Corruption. Humanity. Abel(?). Cain. 2 marks. more corruption.
If Lucifer had kept the mark then would god have let Michael and Lucifer continue with the Apocalypse? Was that god's idea or the angels?
How does it relate to the killing of Abel?
Is the fact that Rowena's Polish boy is (was) now called 'Seth' at all relevant? Did Seth/Oscar have a speaking part in the show?
Where did the mark go? Is it destroyed?
What does the Darkness(!!!) actually do?
If the world is reduced to chaos will we actually see any practical difference in the story writing next season?
Isn't this a good point? (Ref E): As soon as Sam agreed that Dean was right to wanting him dead didn't that actually show that Sam WOULD stop looking and do what was right of the greater good? So in that moment that Sam accepted his death the entire need for killing him evaporated... so no need to kill him after all because he had just shown that he WOULD listen to "reason" and not go to the ends of the earth to save Dean.
So what does 'worthy to bear the mark' mean with this new information about the mark's history?
Why did it matter that the impala's wheel should get stuck in a pothole? Is there somehow a suggestion that the darkness will only get so far? Were they expecting to out-run the darkness somehow?
Was Dean killing at all the reason the mark was getting worse? If so why could he not have hidden away somewhere and tended bees?
Was killing Cain the reason why Dean tipped over tot he side where he was going to continue to get worse no matter what?
Doesn't that mean that Charlie's death was just an excuse for the rampage that would have happened eventually anyway?
In that case wasn't it absolutely necessary that a cure was found for the mark?
Since they only found one cure wasn't that the right thing to do?
Could Rowena have found a cure another way?
So the use of the book actually DIDN'T have biblical effects? That means Sam was right when he said that nobody could tell him what the consequences would be. The consequences of the book itself were relatively minor, except for the sacrificing of a person - Seth/Oscar - which is on Castiel's hands if any of the good guys has to be blamed for it.
How come Rowena could escape? Was it because Sam agreed to her conditions?
Will THE DARKNESS!!! turn out to be a small localised amount of terrorism by a big hair band and the ACTUAL big bad next season (ie for 3-4 episodes) be Rowena?
Why would Death stand within scythe's reach of Dean?