If you manage to nail a first entry of anything out the gate, praise to you. The very fact that game mechanics, storylines, intentions of the development team and budgetary concerns actually match up in a way that's not a total car wreck is a miracle every time. Every single time.
That said, once something does take off, you've got to start planning sequels and maybe even third instalments, and that's where things get tricky (just ask The Matrix). Getting a project off the ground in the gaming industry is trickier than most thanks to the sheer cost of development, let alone something like Mass Effect that was always meant to be more than one release.
You need only look to Silicon Knights' disastrous Too Human franchise to get a feel for how severely bad something can go when that initial first game doesn't land as it's supposed to - a sensation that can transfer across to the big final instalment, too.
If you can't wrap up your story and finish with a bang, that's one hell of a sour taste that in many cases ends up defining an entire franchise forever.