First things first. Before we ever colonize the stars we have a long way to go to colonize our own star. So, I don't foresee much out of our solar system for some hundreds of years. After we have a trillion human being living off planet in the solar system, we will be able to afford to cross the vast distances to other systems. Some of these systems may be a lot closer than currently thought (cool suns, brown dwarfs...). Of course this all assumes we don't go through some kind of singularity which removes the desire, or reason to colonize the currently visible physical universe (do we find the answer to the fermi paradox?). Given we do decide to seed other star systems then, I don't we would ever have to launch "generational ships" in the sense of the original fiction. I think there will be better options and I think true practicality of the concept is pretty problematic anyway.

There have been some tantalizing advances in putting higher mammals into hibernative modes lately. It is reasonable to think that this might be perfected to slow human metabolism a couple of orders of magnitude. A robotic probe containing incubators might be able to bootstrap an entire ecosystem upon arrival from an ark of frozen embryos genetic materials. Nanosystems might be able to bootstrap a technological base once appropriate resources are located and made available. Some level of transmission back to a teeming home solar system after arrival could probably pay for the voyage in terms of pure entertainment value.

There might have to be a skeleton crew at some level of consciousness. They could spend a great deal of time enjoying their own world inside a virtual reality. Continuous communication from earth with use of high powered lasers could keep crew somewhat updated, and could also upgrade software/information components of the vessel.
Most of these things have been explored in (science fiction) literature, and really aren't unreasonable to extrapolate from current technologies.