1. Several of the less significant main Houses are simplified for the TV series. The only Martell child mentioned is Trystane, omitting his older siblings Arianne and Quentyn. Oberon Martell has only 3 bastard daughters rather than 8, half of which are still children. Victarion Greyjoy is left out. In the books, Loras Tyrell has 2 older brothers, one of which is already married, which makes the House more able to turn a blind eye to his sexuality. Davos also has 7 sons in the books but only one in the TV series.
2. Several of the younger characters' ages are raised in the TV series. At the beginning, Dany is 17 rather than 14. Jon and Robb are approximately 18, while Bran is 10 instead of 7 and Rickon is 6 instead of 3. Robert's Rebellion occurred more than 15 years before the main story.
3. The TV series, unlike the books, is not tied to specific character POVs. This enables it to reveal information which is only implied in the books, such as Renly and Loras' relationship, and information which is learned second-hand in the books, like Robb's battles and his marriage.
4. In the TV series, Cersei claims that she and Robert had a black haired son who died in infancy. She and Robert later have a conversation about the boy. However, in the books, she admits that she uses alternate sex acts to ensure that she doesn't conceive Robert's child, and that the one time he did make her pregnant she terminated it.
5. In the books, Robb marries Jeyne Westerling, the daughter of a Lannister bannerman. However, in the TV series he marries Talisa, a travelling healer originally from Volantis. Jeyne does not become pregnant, since her mother, aware of how dangerous the marriage could prove, is secretly giving her a contraceptive tea disguised as a fertility potion. She does not attend the Red Wedding as is not killed.
6. The Battle of the Blackwater is simplified in the TV series. There is only one ship loaded with wildfire instead of sacrificing the majority of the royal fleet. There is also no chain and no bridge of ruined boats. Tyrion is scarred across his face instead of losing part of his nose.
7. In the books, Shae is first hidden in a manse in the city. She is then brought into the castle as a maidservant for Lollys Stokeworth, a plain and slow-witted woman who is gang-raped and impregnated during the riot. Shae becomes Sansa's maidservant after Tyrion's wedding. In the TV series, Shae becomes Sansa's maidservant immediately as the character of Lollys is omitted. It is also a whore named Ros who is threatened by Cersei, instead of Alayaya, a younger whore whose services Tyrion would pretend to buy when visiting Shae.
8. In the books, Tyrion learns that his first wife, Tysha, had truly been the crofter's daughter she'd claimed to be, not a whore. Jaime confesses this lie when he frees his brother. In retaliation, Tyrion reveals Cersei's infidelity and falsely admits to Joffrey's murder. Part of the reason Tyrion kills his father is because Tywin continues to refer to Tysha as a whore during their confrontation.
9. The majority of Tyrion's journey through Essos is omitted in the TV series. He doesn't travel with Jon Connington and Young Griff/Aegon, as this entire story-line is cut. It is Jorah Mormont who is infected with greyscale, rather than Connington, and this takes place in Valyria rather than in the Rhoyne ruins.
10. In the books, there are several wildling characters who were left out from the TV series, including Mance Rayder's newborn son, his wife and her sister Val. The boy is swapped with Gilly's son in order to prevent Melisandre from potentially sacrificing him for his king's blood. Mance is also not killed - Melisandre burned Rattleshirt instead, made to appear as Mance using an illusion. Mance later infiltrates Winterfell with a group of wildling women in an attempt to rescue Arya Stark.
11. Sansa and Theon's story-lines are combined in season 5 of the show. Instead remaining in the Vale throughout, it is she who marries Ramsey Bolton. In the books it is her friend Jeyne Poole, who is being passed off as Arya, who becomes Ramsey's wife and victim.
12. Cersei's plan to attack the Tyrells is different in the books. She first tries to tempt Maegery into committing adultery with a Kingsguard, then frames her of this treason when the seduction attempt fails. This makes Cersei's own downfall more ironic and fitting. In the TV series, she exposes Loras' sexuality to the Faith, portraying Westerosi society as being more homophobic than in the books.
13. The Dornish story-line also differs in the books. Oberon's older daughters suggest various methods of punishing the Lannisters for his death, and are imprisoned by their uncle Doran to prevent them from taking action. His daughter and heir, Arianne, attempts to crown Myrcella in order to incite war and also cement her own claim to Dorne. After this fails, Doran explains the truth to her - that Dorne has been secretly allied to the Targaryens for years, that she had previously been betrothed to Vicerys before his death, and that the oldest of her brothers is travelling to meet Dany and propose a marriage alliance. However, Dany rejects Quentyn and he is killed by her dragons when he attempts to steal them.
14. In the books, Euron Greyjoy possesses a dragonbinding horn, taken from the ruins of Valyria, who he plans to use in order to control one of Daenerys' dragons. He sends his younger brother, Victarion, to Essos to do this and to bring Dany to him. However, Victarion plans to claim Dany himself, in revenge for Euron previously impregnating his wife and effectively forcing him to kill her.
15. In the books, Catelyn's body is recovered by Nymeria and she is revived by Beric Dondarrion, sacrificing himself to do so. Her body is partially decayed and she can barely speak since her throat was slit so deeply. She then leads the Brotherhood of Banners as Lady Stoneheart. During A Dance Of Dragons, she captures Brienne and Pod, and threatens to hang both unless Brienne kills Jaime Lannister.
16. The reaction of the North to the Boltons and Freys is more complex in the books. Several of the bannermen remain secretly loyal to the Starks and remember their own losses at the Red Wedding. Lord Manderly sends Davos Seaworth to retrieve Rickon Stark, believed to be hiding in Skagos, after pretending to have the man executed. There may also be a plan to reveal that Robb Stark had legitimised Jon Snow and named him as his heir before his death.