Ok so I still haven't done any main missions outside of the initial tutorial, I have however spent 6hrs running around doing Assassination and Arms Dealer missions. I'm no game designer but like many others I've found the road blocks and random encounters a little annoying. I think random encounters are ok, I don't really have any complaints with them but continually being shot to pieces at road blocks is annoying. In these instances I believe they could easily have made it so that these road blocks could at least be 'bought' in the sense you could hire guys to watch those areas for you rather than continually respawning enemies at them.
The other part is there really should have been a quick travel. Each mission I've done so far has required me to travel at least half a maps distance. Ok, so I have been scouting and unlocking every safe house en route during my side missions but I'm at 6hrs of play and 7 side quests completed, the majority of my time seems to be spent travelling, especially if you lose a vehicle, then it really becomes a time consumer. I don't see why there is no quick travel in the game, I mean they have the buses but they aren't exactly convenient, often by the time I have travelled from the mission start to a bus, arrived at the other bus station and then trekked it to the mission location I'd have pretty much done the same distance just cutting through the guts of the map anyway. You should be able to quick travel to points you've already located. Now I think about it, the Road Blocks would actually make ideal quick spawn locations for travelling.
Otherwise, thoroughly enjoying this game. Gun handling is incredibly solid, real time day / night and weather cycle is fantastic, visuals are gorgeous for a console (playing 360 version) and I like the weapon upgrade system.
Oh and you can run over wildlife, woooooo