Everyone is putting out their wishlist, here is mine, all of these relate to randomgen:
1) Town name discovery with decent bonus XP (XXX Discovered)
2) Fishing, boating, etc.
3) Cars, more vehicles you can drive.
4) Newspaper clippings, books, magazines, etc. that tell the story of what happened. Once the player reads, also log it to the journal and give the player bonus XP. Each clipping could have a date so the player knows when the event happened.
5) Related to the above, the quest system has a ton of potential, it would be great to see it used for something other than hunting/killing.
6) Larger, centralized biomes that more closely follow what earth has IRL. A snow 'island' shouldn't be in the middle of a desert, for instance, and deserts should have fewer bodies of water. Maybe add some oasis type areas. Also, green biomes need more lakes, and frozen areas need frozen lakes. LESS HILLS AND MOUNTAINS. Let's save the mountains and hills for specific regions in randomgen. Relatively lat areas (valleys) should exist between these regions. More lakes/ponds/rivers for the green areas.
7) Built in Dead-is-Dead mode. Maybe a horde survival mode (everyone spawns together, every night is horde night, hordes get larger and more powerful every night, Players try to survive together as long as possible)
8) Simple RESTful API for pulling player stats out of the game. (useful for #7).
9) Roaming hordes should not spawn and target players. Roaming hordes should always exist, always be roaming, and only find the player if they stumble across the player and/or base on accident or the player is doing something that generates smell (campfires, forges, etc.)
Better roads. Who builds up a cliff *JUST* to put roads on?!

Most roads are built AROUND rough terrain. Also, the roads need lines. Old alphas had this in some areas.
10) Cold snowy areas, hot deserts. This is already somewhat implemented, but the cold areas STILL get rather warm for an area with snow on the ground 24/7. The desert/snow biomes should bring challenges of their own in the form of climate.
11) Weather systems instead of RNG weather. Seasons that bring challenges of their own, etc.
12) Sync up the multiplayer dedicated server and local multiplayer code. There are many bugs that exist in one that do not exist in the other, and some mechanics seem completely different.
13) Multi-core optimizations!
14) Better management of remote connections. (I have a 30ms connection to a dedicated server and it feels completely different than my local multiplayer server. Part of that could be from #12 though.)
These are a bit further out there:
1) Increase of the complexity of the crafting system! Why this was ever changed I'll never know. Example: Wood -> Logs -> planks or sticks! (YES! I SAID IT! STICKS!!!!!!)
2) Region based housing/architecture. Example: compare a house in southern CA or AZ to one in the northeast. A world of difference.
3) More rural housing, again: Not cabins, but full on actual houses like you see IRL.
4) Maybe consider having the larger cities *only* spawn in the wasteland. Small/midsized towns still spawn everywhere. Also, instead of zombie bears spawn in the wasteland, have them spawn in the forest biome (not the greener one, but the darker one, I can't remember what they are called these days) Compensate for this by making it so the wasteland has significantly more zombies, and make them RUN! Also, landmines in the wasteland? Is there a reason for that? As I imagine a wasteland type area, it used to be a dense urban area at one point, not a military war zone. Maybe TFP has backstory in mind.