I like where this is going: wilderness reclaiming the urban ruins, nature recovering from the mass-destruction the Industrial Age has caused to it, but nature tainted by the legacy of civilization - nuclear powerplant meltdowns (what would happen if the human operators of a nuke plant die and no replacements arrive?), toxic waste with long half-lives, vast tracts of urban ruins slowly re-colonized by nature. A very large (and welcome) divergance from the archetypical "the world got nuked and it's a Wild-West style desert" paradigm of many post-apocalyptic books/films/computer games.
A point which you should consider is how much remaining useful products (light industrial machinery, weapons, ammo, medicine, vehicles, fuel and so on) would still be around 300 years after the Apocalypse. A mostly-biological Apocalypse would mean that most booty won't be damaged by the war, so most losses wouldbe due to natural erosion - this rate of erosion is an interesting point for our science experts to chew at
) - but won't this small population have access to ALOT of loot to scavange, especially easily-operated things such as small arms and body armor?
Also, for an 2070-Apocalypse setting, you might be able to use some of the space-colonists (from a self-sustaining colony, robably on Mars) as either the PCs (trying to find unreplicatable spare parts for whatever broken McGuffin in the colony, for example), as a plot tool (a shuttle has crashed near the PCs village and the survivors hire/convince/force them to help them reach a spaceport/extraction-point/etc, or as the main antagonists (either conducting experiments on Earth survivors to see how their biology has reacted to the effects of the bioweapon and yet survived, or even trying to use their relic-technology to enslave Earth survivors to use as slaves to rebuild civilization with the Colonists as the rulers).
And, for a hard-science approach to "Zombies", you couls have a genetically-modified strain of Rabies (sp?) infecting human survivors in more recent times (perhaps a tribe unknowingly entering a bioweapon lab?); they won't be dead, but other zombie-like behaviours could easily be manufactured (BRAAAAAIIIIIINNS!
).
I had a similar idea some time ago. My idea was that about 20 years into the future, after a period of rapid advancement in biotechnology, an ecological catastrophe (think West Antarctica melting over a few years due to global warming, combined with very unstable weather everywhere) puts the spark to the powderkeg of depleted non-renewable resources. This ended up with a limited nuclear exchange, but far wider bioweapon and chemical exchanges, with about 95% of Humanity dying (some from the bioweapons, some from famine and disease coming in the wake of the death of civilization). This would mean a global population of 500 millions (population growth would easily give us 10 billions in a few decades), somewhat similar to the pre-industrial or early-industrial population of Earth. Due to the mostly Human-specific nature of the destruction, Nature in general, and plant-life in particular, would recover far faster than Humanity even with all the climate-change mess going around. The game would be set 50 years after the catastrophe, with most bioweapons no longer active for atleast 30 years, and with the larger shelters (which have existed for two generations with closed life-support environments) starting to open up. On the surface they'll encounter nature gone wild, non-sheltered Human survivors (usually naturally immune to the bioweapon used in their area) gone semi-wild, some remaining robotic systems (rare due to the lack of maintainance for 50 years), and... "monsters". These monsters would be genetically-modified animals designed during the Biotech Bubble for various purposes, including used as beasts of war or farm animals. Think of bio-modded attack dogs, rats genetically-engineered to be larger and more vicious to infiltrate the enemy's maintainance ducts and chew away the cables and pipes there, large cockroaches genetically engineered as a high-sustainability source of meat... Technology would be pre-industrial in most surface-survivors communities, with a few of the larger ones reagining some early-industrial capabilities; tech-scavanging would be common; the sealed shelters would ahve their own pre-war stashed gear and some light industrial equipment, as well as the knowhow to operate it, but would typically have very small populations of a few thousands each at most. I might end up running this setting to my girlfriend (who've already expressed an interest in post-apocalyptic settings similar to this) using a derivative of the
FUDGE system or, maybe, modified CT rules.