This is my 3rd play through, which I'm a good ways into, and not once have I thought about fully upgrading a weapon to get infinite ammo (if that's what you mean OP). So no, I don't base replay value on weapon upgrades. I don't even base it on the bonus stuff you can get with CP (not so far anyway), as I've yet to even use such items. I'm more focused on improving basic strategies, like maximizing funds and ammo via upgrading capacity only when the mags are empty, knowing where all the Magnum ammo is (you'd be surprised how many miss the two rounds at the Altar before the final boss), and calculating what optional bosses I can kill.
One of the things I really respect about the game's design, despite some ridiculing it, is that although you can now buy ammo, The Duke never has much to sell, except for handgun ammo. This forces you to maximize your ammo by the means mentioned, and hitting your shots, and picking the best moments and places to shoot, like after the Mill Giant drops down, and his head goes still for a bit.
Sure, there's a lot to the game, especially considering it's length, but there's also a lot to know about just gameplay tactics, aside from all the bonus stuff. This and things like adding more enemies and increasing their speed on the hardest difficulty mode are what really adds replay value best to me.