What is the weakest synergy in the game?

Pirates,

They give no actual combat bonuses

Or early hextech

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Pirates,

They give no actual combat bonuses

Or early hextech

Synergy meaning buff combination, not just individual buff. But you still aren't wrong with your response, because...

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Pirate + Hextech. If your build revolves around getting those two buffs, you don't actually have any combat buffs. Now of course if you take Graves and Gangplank as 2 of your pirates, (instead of one of them and Pyke + TF) you can easily get Gunslingers as well, not to mention adding MF once late enough.

Nobles are very strong early game, super weak mid game and super strong late game. Blade masters and wilds are the same as well.

While pirates alone (even with gunner2 w/ gp and graves) is weak for combat, they make up for the inevitable loss of hp during late game with lots of gold advantage over your opponents. It would depend on you on how to make use of that gold.

You need to transition in and out of different synergies throughout the game and be exchanging units.

knights, exept for the early game, but they fall off quickly and their lategame is ingorable even with 6 knights. Only exeption is when paired with nobles, or with guardians vs physical, and even then the knight boost isn't that huge.

Else, ranger 2 is pretty bad as it's just so unreliable, though 4 rangers is a strong synergie. Similar for glacial, two glacials can sometimes win a fight, and sometimes do nothing at all, you need atleast 4 to have any reliable benefit. Shapeshifter boni also is also a bit wierd, If your shapeshifters are atleast lvl 2 or have solid items, it can be very strong, but if not they often die befor transforming and get no use at all from it(also, fuck kassadin).

Weakest synergy is arguably brawler (I know this is antithesis to what most people think, because a lot of comps use brawlers; but that's because of their other traits/skills, not the HP Gain.)

There's a direct counter to brawler builds (Burn) and the lack a lot of CC map control. If you can build bleeds, or aoe skills as a team, generally brawler will always fall apart end game.

Pirate is probably #2 weakest, because it frankly has no combat use, and its members fall off (GP works better in Gun/Blade teams), and players overspecialize in it.

Pirate

It requires you to pick Graves and/or Gangplank (the worst picks in this mode)