The third one is really big. The Romans lost a lot of territory in Anatolia between 1180 and 1204. And of course the power struggle between claimants ultimately led to the Crusaders sacking Constantinople.
I blame Manuel I Komnenos. His reign (1143-1180) was largely a magnificent failure in the end.
While the armies and fleets he commanded were vast and impressive, he failed to use them effectively. The wealth at his reach was enormous, yet he did not spend it wisely. His diplomatic efforts were extensive and wide-ranging, yet they brought no lasting benefit to the empire.
His military efforts touched every possible direction, yet he failed in most of his wars/campaigns. Here is a list of the wars/campaigns during his reign:
Anatolia 1140s - failure
Second Crusade 1140s - failure
Italy 1150s - failure
Cilicia 1150s - success
Hungary 1160s - success
Egypt - 1160s failure
Anatolia 1170s - failure
We cannot reasonably expect more than 3 good emperors in a row, and the three Komnenoi (Alexios, John II, Manuel) together ruled from 1081 to 1180. It's inherent in the nature of monarchy that you won't get one good ruler after another and maintain it for more than a century. Sooner or later you'll get a bad emperor.
Manuel's diplomacy, and foreign policy in general, was rather unsuccessful in the end. He could have managed the Second Crusade differently, but instead of putting his whole heart into it and using it as an opportunity to make real gains, he treacherously made a truce with the Turks and did not participate in the campaign. This was a major blunder, in my opinion, and the failure of the crusade did permanent damage to Byzantium's reputation, particularly as the Byzantines were accused of aiding the Turks (which may or may not be true).
His failed war in Italy was extravagantly expensive, wasting vast quantities of gold on a project that completely failed in all its objectives. Given the empire's rapid collapse after 1180, it's only natural to think the gold might have been better spent elsewhere.
His expedition to Cilicia and triumphal entry into Antioch was a success in the 1150s, and he did win a war with Hungary decisively in the 1160s. These victories did add some strength to the imperial army (Hungary became a vassal and had to provide troops) and possibly some wealth and prestige (Antioch became a vassal and also provided troops, and Cilica was added to the empire).
However the invasion of Egypt in the 1160s was another costly failure, and is difficult to justify given that it relied on the unreliable help of reluctant Cruader "allies" who often behaved more like enemies, and that it was prioritised over the situation in Anatolia, which was far more relevant to the empire's interests.
This is of course compounded by the failure in Anatolia in the 1176 campaign against Konya, where Manuel's army was famously defeated at the battle of Myriokephalon. The failure of that campaign really gave the lie to the imperial pretensions of the court in Constantinople. The Sultan of Rum demanded that the emperor demolish two fortresses; Manuel complied with this demand in the case of the one but did not in the case of the other. But the mere fact of failure of this impressive and costly expedition, combined with the emperor taking orders from the upstart Sultan of Konya, was a major humiliation to Byzantine prestige and credibility.
The arrest of all the Venetians in the empire in the 1170s and the confiscation of all their property was another foolish move by Manuel. This alienated one of the most useful allies of the Byzantine Empire, with results that would prove to be disastrous in 1204 when a Venetian fleet arrived in Constantinople and sacked the city, dismantling the empire.
The biggest failure of Manuel is that he failed utterly in Anatolia. His reign was the empire's last chance to retake the interior, and he clearly had the manpower and the money to achieve this. But instead of campaigning effectively to achieve his goals, he allowed the Turks 30 years to build up a unified state (the Danishmends and Seljuks had been two separate, divided and weak domains at the start of his reign). He then compounded that failure by losing at Myriokephalon.
Really, for the empire to have succeeded in this period, it would have been necessary to take Konya and Ankara. Doing so would have secured the Byzantine position in Anatolia, allowing the provinces to prosper. It would also have halted the Turkification and Islamisation of the region. The capture of the Seljuk capital would likely have ended their state, since the Danishmend regions would probably have rebelled and returned to autonomy. In such a case, it would have been a relatively simply matter to mop up the remaining cities of Anatolia and restore the frontier to its ancient defensible position on the Taurus mountains. Even if the empire failed to do this, it would have been facing a greatly weakened enemy, from a position of much improved territorial control. Byzantine Anatolia would have been in a much better position to survive and prosper than OTL.
Instead, Manuel largely squandered the opportunities open to him. It is a pity, because the Byzantine Empire was never again to be in a position where its survival as a great power could have been as readily assured.