Depends on which "prediction" are you talking about. As you know, there are several variables/console commands that regulate prediction.
PredictionFoe is for frag, but also the PredictionFilter, PredictRemotePlayers and MaxPredictionSteps.
I remember
changes.txt wrote that PredictionFilter must be set less than 1 or else
"entities will run out of control".
When I had the bad sync issue, I didn't solve anything after I set PredictionFilter less than 1 or directly equal to 0. I set the hotkeys for enabling Prediction/PredictionSteps (in this case, the values from 1 to 3)/PredictionFilter while playing but I still had the issue. I have to dig into my
"SeriousSam - Copia.log" in which I save most of the logs if they have something relevant, because it was 2 or 3 months ago.
The PredictionSteps were the reason of fake kills, resurrections (both killed players and Coop monsters), teleports, graphical glitches of 3rd person view sprite while walking/running, etc...
The PredictionFlushing is another variable which I didn't discover what is about, yet.
Anyway, I have all the prediction commands set to 0 (see first post of this thread) by default on my netsettings script; and since I deleted PersistentSymbols, weeks ago, I don't have this issue anymore (for now).
But, yes: prediction OFF (/cli_bPrediction=0) could be a possible cause. But I think nothing would change for me, prediction ON or OFF; I still have to use my "personal" prediction: try to shoot before if an opponent is going to a predictable direction. The problem are the experienced players who also have stable ping (due to fiber?) and move in a less predictable way. And this is valid for every arena shooter I've been playing, even Quake.
This is the most interesting consideration.
Serious Sam, at least the classic one, seems to work like a Doom, Quake 1996, Duke Nukem 3D, Soldier of Fortune 1 (made using Quake 2 engine), you can notice this by even playing with bots offline (deathmatch mode of course, not single player Coop/storyline). Maybe that's why it is so difficult to aim (especially with Sniper/Double Shotgun) in frag (whereas Coop monsters are pretty easy to aim at).
Serious Sam HD and Quake Live are more "immediate".