Hi all - long time reader, first time poster, but as I'm writing a thesis on Johnny K this is pretty much when I thought I should get involved...
Lots of this depends on which sources you believe, as according to Kinnamos, John intended on making "Cilicia and Antioch along with Attaleia and Cyprus" into a 'portion' of the empire for Manuel, and him raised to be a Latinophile would support this, as it would keep the Latin population onside and having it seem as separate to the empire for a generation would allow them to get used to the idea of 'Greek' overlordship - though it would be unique in the history of the empire since classical times at least to give a large part of the empire into the care of another son.
There is however another chronicle (thus far only in a German edition) that mentions that John had the original plan to put his sons on the thrones of the world, including the young Alexios in Old Rome and Andronikos in Jerusalem, though whether this has any truth in it is anyone's guess.
Generally, regarding the succession, it is definitely not clear who John favoured once Alexios and Andronikos were dead, as though Manuel's entrance into the imperial tent and then emerging saying he had been acclaimed the heir is suspicious, John's best friend and Grand Domestikos John Axouch hurrying back to Constantinople to secure Issac so that Manuel could take power does suggest he was operating on the orders of his friend, as a few years later he gets drunks and says maybe Issac would have been better at a dinner implies he wouldn't have done this unless John had told him so. Your idea of Manuel as 'flavour of the month' definitely holds weight though, as if he hadn't have been acclaimed Emperor the army would likely have broken up and caused no end of chaos, so it was the only option really. The AIMA prophecy however only really becomes a big deal under Manuel as the primary source evidence for it is sketchy (and may even have been fabricated by Manuel) so I wouldn't bring that under too much consideration.
Your marriage to Agnes of Courtnay idea is also problematic as Issac's first wife Theadora doesn't die till 1144, and if anyone was going to be married to a Latin in the area it would have been Manuel (he was originally meant to marry the heiress of Antioch, and those negotiations falling through when she married Raymond helped cause John's first expedition) - the negotiations with Bertha of Sulzbach are ongoing but then there are plenty of imperial princes around for anyone to marry so some sort of alliance could definitely have been done.
On to the POD of John not dying though - court rhetoric in the form of speeches and poetry had already put forward the message that Edessa, Antioch and even Tripoli acclaimed John as their overlord after the first campaign, and with the threat of Zengi now in the wings, that becoming more of a reality was definitely a possibility. John has no problem with the Serbians ruling independently for example, as long as they consult him on the succession, send troops when he asks for it, have orthodox bishops, use byzantine laws and coins, and acclaim him Emperor he has no problem with whatever else they do (think of these areas more as commonwealth realms rather than fully integrated states).
As such, were he not to die on his hunting trip (which in itself was likely a PR measure to keep the Cilician nobility onside), he would likely have had a punitive campaign on the frontiers with Antioch and Edessa (and possibly Cilician nobles) in tow, which if successful may have extended the frontier somewhat, but if not he would at least have been left with more loyal vassals in the area along with some plunder as in the first expedition. His next campaign however would almost certainly have been against Ikonion.
His previous campaign securing Lake Pousgous in 1142 already put him within striking range - Dorylaeum had already been fought over a few times (even Alexios had won here in his last campaign, Philomelion is the plain between Dorylaeum and Ikonion) and John had won victories there recently, but not held and refortified it, as the lake is much better if you want to strike against a weakened Ikonion that has no allies to the north. Manuel's Ikonion campaign (one of his first acts once he was secure in power in 1145-6) was almost successful until Mas'ud managed to find those very allies. He was only able to do this because by then he had started to be on the winning side of the Danishmend civil war through allying with Ibrahim Danishmend, the recently departed Mohammed's eldest son. If you take that campaign a year or three earlier however, you have a civil war involving Mohammed Danishmend's three sons, his son in law Mas'ud of Ikonion, and Mohammed's three brothers and their three sons going on in Anatolia, which only became a three way civil war rather than a seven+ way civil war about a year in. John therefore could easily have taken advantage of this general chaos to take at least Ikonion, which would then have changed the shape of the civil war and therefore the empire's future campaigns massively. Equally Demetrios of Georgia may have had more success against the Turks on his borders, weakening them further. John not dying also means that Thoros of Armenia likely doesnt escape house arrest in Constantinople and therefore that region may become less troublesome in future. In general, the Romans retaking Anatolia without the need for a crusade is much more likely in this scenario, regardless of John's successor.
How this would all affect the eastern frontier and the fall of Edessa is difficult, as with John living longer Zengi may well have chosen softer targets, but equally may have taken advantage of John being at war in Anatolia to take Edessa as OTL. Though I'm fence-sitting on this, it would depend on whether John carries through on his intention to go to Jerusalem, or whether he focuses on Anatolia, as the former would likely have kept Edessa in Christian hands, and the latter would allow Zengi to take it. The former could well mean no second crusade in a recognisable form, which would change a lot.
If it had happened, then the Emperor (whether Isaac or Manuel) may well have 'marched with the crusade', but likely would have commanded a separate part of it. It is often forgotten in the Frankish accounts of the first crusade that there were three armies, one commanded by Alexios, and they were all driving to the East, but all ended up taking different targets. If the second crusade was marching through, then the Emperor would likely have commanded one of the contingents while westerners commanded others, either way the crusade was likely to result in better gains, particularly due to the good relationship between the Germans and Romans at this point. Depending on Zengi surviving, retaking Edessa and then going on to take Aleppo with the French, Germans and Romans working together could well have occurred.
If it hadnt happened, and if the Norman invasion of Corfu went OTL and John is still in good health (and there's no reason to suggest he wouldn't be), then the possibility of earlier imperial intervention into Italy is on the table. Imperial troops had supported Lothair on the ground in Italy in 1136 and Naples still professed ostensible eastern imperial loyalty until the same year (both John VI and Sergius VII held the imperial court title of Protosebastos), and with the German alliance and Papal diplomacy still going strong against the Normans, this may well have been the next campaign on the cards at the end of the 1140s.
Overall, there are a lot of 'ifs' here depending on what PODs you have. Johnny K surviving in and of itself almost certainly means greater integration of Antioch and Edessa and more gains in Anatolia however, taking advantage of the Danishmend civil war, and then depending on Zengi either a much more successful 2nd Crusade, or if no 2nd Crusade then the Crusader states likely stay unchanged, and there will be an earlier Roman invasion of southern Italy with the Germans.
If you would like proper sources for all of this then do check out either the PBW:
http://db.pbw.kcl.ac.uk/jsp/index.jsp or this for general family tree information:
http://fmg.ac/Projects/MedLands/CONTENTS.htm, or if you give me a few years, my possible book on Johnny K...