Because I'm pretty swamped with freelancing, I only played it for about an hour and a half last night, but it's pretty damned awesome. It looks and sounds incredible, and often in very subtle ways (especially the depth of detail, the physics and the lighting effects); the acting, despite the absence of big-name voice actors this time around, is top-notch; the story is pretty fascinating and, as is typical for the franchise, contains lots of really funny moments so far; the music is phenomenal (and the talk show -- and now, TV! -- programs are hilarious); and so far, I like all the changes in play except for a couple of minor ones.
There's a bit too much of the Sims/social development-style stuff for my taste; that stuff is fun, but it can stretch out the gameplay endlessly when you're trying to accomplish story goals. The hand-to-hand combat system is also kinda clunky compared to the previous, stripped-down ones, and it involves a lot of investment of time considering how little you actually do it in the game.
But the targeting dynamic is much improved, the car physics are way better, the load times are practically nonexistent, and there's lots of little stuff that make it more fun to play. While driving around endlessly can be lots of fun, it can also be tedious if there's too much of it, so the ability to hire cabs, take the subway, and skip non-goal-oriented trips is a godsend; the introduction of the GPS as a way to track your route from one marked location to another avoids a HUGE amount of frustration at moments when you're not yet familiar with the map; and the more realistic role-playing stuff, combined with a new feature where, at key moments in the game, you can make multiple choices about how to resolve a situation -- with each choice causing the storyline to branch out differently -- is terrific and makes the human landscape as interesting as the physical one. (For all the talk about killing hookers and stuff, that was never a requirement of the game -- but with this iteration, you can actually be rewarded for not killing people.
I'm not nearly far enough in it to say how good it really is, or if it supplants GTA: San Andreas as the best video game of all time, but so far, it's fairly well kicking my ass. Too bad I blabbed for a week about how excited I was to get it; if I hadn't, I might could have gotten away with taking a sick day today so I could stay home and play for a good 8 hours. B'oh.