I still have very little idea as to what the purpose of the introductory flashback sequence was. Originally I assumed the main plotline would have you searching for Doctor Moreau, with him possibly turning out to be the main antagonist, but there is absolutely no mention of him after the intro (unless I missed something, but if I did then it couldn't have been very vital to the plot). I was also quite confused as to whether or not the character you play as in the intro is meant to be the character you continue to play as in the main game. I suppose it's possible that the character you are playing as in the intro is an earlier clone of yourself, but then what is the point of that.
It then throws an amnesia plot device on top of this, which as it turns out is completely pointless; presumably the reason you'd have an amnesiac protagonist is so they can end up finding out that they, and everyone else in Vault 8 was a clone the whole time, except everyone in Vault 8, including your character, is already kept in the dark about the cloning project, so having them be an amnesiac is completely redundant (compared this to Fallout 1.5, which I thought handled the amnesiac plot device pretty well, even if it was a classic retracing your steps story that is somewhat cliche it works well).
Then you have the sloppy Jay Kukish character, another possible antagonist character that ends up going nowhere. After some buildup all you get is an awkward meeting with him where he then gives you another plot element that has no meaning, the mysterious device, and sends you off to follow some more threads. Then you find him dead in the last area. Who killed him, why, who knows, who cares.
Then the Reaper of Souls. The only reason I knew he was supposed to be the villain was because I saw brief mention of it in the thread before playing, otherwise I would have had no idea what that the first encounter with him was meant to imply. It seems like they were copying the Frank Horrigan encounter for the sake of it, but the original Frank Horrigan encounter was very ominous and immediately lets you know the guy is a psychotic villain, you are also teased with his presence throughout the rest of the game to remind you of the threat, whereas in Nevada you see the Reaper of Souls once in the confused beginnings and then not again until 80 hours or so later at the end of the game.
I'd rant more but I realized I don't really care. I had forgotten about so many of the plot threads by the end of the game anyway. To top it all off there is a shitty final boss fight where my only option was to reload over and over until I got a lucky critical hit with my minigun.
With all that said the game is still worth playing just because everything other than the main story is very good.