A major sin is one that being punished in hell is promised to its committer in the Quran or ahadith. (There are also other criteria for a sin being a major one). Also minor sins turn into major sins when committed repeatedly (when insisted on by the sinner).
In the Quran, Allah has promised to forgive all sins if one truly repents to him. Regarding Haqqullah (Obligation to Allah) repentance would be to make up for the past and saying Istiqfar while regarding Haqqunnas (Obligation to people) it would be doing Istiqfar, giving the person back his rights and striving to obtain his satisfaction.
There are several opinions as to what exactly makes a sin major:
1- All sins that the Quran or Hadith clearly mention as major ones.
3- All sins which are considered greater in the Quran and Ahadith than sins that are indisputably known as major ones.
4- Any sin that is considered great from the believers' point of view in a way that one can be sure that this greatness was acknowledged since the time of an infallible.
5- All sins are major sins; because the greatness or smallness of a sin should not be considered as it is mentioned in some Ahadith, instead one must consider the greatness of the one who has been disobeyed. In this regard Imam Sadiq says: "Do not consider the smallness of a sin, instead consider whom you have disobeyed."
Of course those who have categorized sins into major and minor sins also believe that minor sins can turn in to major ones in certain situations:
1- Insisting on committing minor sins (Repeating minor sins): The prophet says: "There is no major sin (and it will be forgiven) after repenting (from committing major sins) and no minor sin (it turns in to a major sin) after insistence (on committing and repeating it)."
2- Underestimating a sin, Imam Ali said: "The greatest sin is one that a person considers to be small".
3- Being glad for committing a sin, the prophet said: "One who commits a sin and is happy about it will enter hell while crying."
As for the forgiveness of major sins, the Quran says: "Say [that Allah declares,]" O My servants who have committed excesses against their own souls, do not despair of the mercy of Allah. Indeed Allah will forgive all sins. Indeed He is the All-forgiving, the All-merciful."
The late Allamah Tabatabei has narrated that Imam Baqir considered this verse the most hope inspiring in the Quran.
On one hand this verse covers all sins including shirk (Associating others with Allah) and on the other hand we know that shirk is only forgiven by repentance, therefore we have no choice but to conclude that the mentioned verse only applies to those who repent; because forgiving the sins of any individual must have a cause, and the Quran has mentioned two causes for forgiveness: 1- Intercession 2- Repentance. The abovementioned verse that addresses all people, Muslims and mushriks, is definitely not about intercession because it is clearly stated in several Quranic verses that intercession does not cover the sin of Shirk. Therefore the only option remaining is repentance. Also, Allah has clearly declared that he will forgive all sins, even Shirk, if one repents.
The way of repenting for sins can differ, because some major sins are Haqqullah while others are Haqqunnas.
In order to repent from a sin that is Haqqullah one must truly regret his previous deeds and decide not to return to his sins. Also he must make up for his deeds if possible, like making up for the fasting and praying he has not performed. And in order to repent for a Haqqunnas sin, in addition to regretting previous sins one must give back the person’s right unless that person overlooks his wrongdoing and doesn’t want compensation.
In this regard Imam Baqir says: "One who is martyred in the path of Allah is purified from all sins except for the debt he has to repay which has no atonement, either his debt needs to be paid or the lender needs to forgive his debt."
Based on Quranic verses and the Ahadith, Shahid Dastghaib held that: "True regret and remorse entails an effort to compensate; meaning that if it is haqqullah, like praying, fasting, paying Zakat or performing Hajj, he must make up for it. And if it is haqqunnas and relates to financial issues he must repay the rightful owner or his inheritors if he is no longer alive, and if it relates to someone’s respect and dignity, he must ask that person for forgiveness. Also if that person has the right to do Qisas (retaliation) or request Diyah (blood money) the sinner must submit to his choice."
Therefore inshaAllah, all sins, whether they are Haqqullah or Haqqunnas, will be forgiven if one truly repents and makes up for them accordingly.
 Dastghaib, Abdul-Husayn, Gonahane Kabireh, vol. 1, pg. 26.
 Lawami’ of SahebQarani, vol. 2, pg. 368.
 "لا تنظرو الی صغر الذنب و لکن انظروا الی من اجتر أتم" Mizan al-Hikmah, hadith 6602.
 Dastghaib, Abdul-Husayn, Gonahane Kabireh, vol. 2, pp. 273-279.
 "لا کبیر مع الاستغفار و لا صغیر مع الاصرار" ReyShahri, Mizan al-Hikmah, hadith 6617.
 "اشد الذنوب عندالله سبحانه ما استهان به راکبه. Ibid, hadith 6562.
 "من اذنب ذنباً و هو ضاحک دخل النار" Gonahane Kabireh, pg. 280; Bihar al-Anwar, vol. 6, pg. 36.
 Zumar:53 " یا عبادی الذیناسرفوا علی انفسهم لا تقنطوا من رحمة الله ان الله یغفر الذنوب جمیعاً ".
 Translation of Al-Mizan, vol. 20, pg. 526.
 Ibid, vol. 17, pg. 425.
":" کل ذنب یکفره القتل فی سبیل الله الا الدین لاکفاره له الا ادائه او یقضی صاحبه او یعفوا الذی له الحق " Gonahane Kabireh, vol. 2, pg. 6 (Kafi, vol. 5, pg. 94, chapter of ‘Deyn’, pg. 93).
 Ibid, vol. 2, pg. 434.