Are there any tangible, genuine downsides to ignoring your "friends" in GTA 4? I found the whole friend/girlfriend system to be somewhat annoying and detracting from the game itself, and if I decide to go through it again, I'd like to just bypass all of that. (Well, aside from the critical girlfriend in the beginning of the game, and just enough with Jacob to get the gun delivery service.)
You miss out on the perks, like the weapon delivery you mention. Also there are Achievements & or Trophies depending on what platform you're playing on.
After that, I do not believe so. I think (but need to verify) that as you ignore them how much they like you will drop, and if it drops too low they won't be your friend anymore if you change your mind and want their friendship after all.
Still, my thought would be, on a second playthrough, don't worry about the ones you don't care about.