Negatives?
Every 100 point character is actually a 145 point character with -45 points of disadvantages. The bulk of these that can reasonably be taken by an adventuring type fall into the "mental" category - and in order to make sure these role-playing disadvantages have a sufficient impact on gameplay, they are exaggerated to the point where they go far beyond personality traits or quirks and into the realm of mental illness.
In every GURPS game I've played (admittedly, I haven't played in many) the characters were basket cases - compulsive liars or thieves, characters with no sense of humor whatsoever, bad-tempered lunatics with a good chance of flipping out every other time things got heated in negotiations (gee, when does that ever happen in a typical adventure, eh?

), people with crippling phobias... Even if taken at lower levels, this means the character ends up with several mild mental conditions, that would probably make life miserable for an everyday shmuck with an undemanding job, never mind an adventurer dealing with high stress levels...
Then there are the so-called "balanced" characters... It's nice that everyone is supposed to be equal, built on a 100 points, but it means that, despite the vaunted flexibility, many character types aren't possible, only caricatures. 100 points are not a lot, so if you're (reasonably) strong and tough, there's no way you'll be smart, or fast, and vice versa... No way to play a big, burly mage, for example. In GURPS the average strength for a 6'1" man is listed as 14, which costs 45 of the 100 starting points... Let's say, hypothetically, that I'm 6'1", of average strength for my height, at least as smart as I am strong (compared to an average guy), and slightly more dextrous and sturdy than average. This means two 14's and two 11's - costing 110 points, and that's without any skills factored in. A college graduate with a degree in a hard science will probably have a good 15 or 20 points of skills relating to his chosen field of study alone. A 100 point character is nobody special, and while you can, theoretically, increase this number, many people will raise the cry of "munchkin" at this, and, because of the way advantages are priced, once you have more points to play with it does get easier to break the system.
Then there is the combat system with the 1-second (yes, that's ONE second) combat round, which requires you to declare actions to change facing, ready a swing with a wepaon, nock an arrow, etc. - while it is a nicely done system, it is much too detailed and, because of the myriad of detail, too slow for many people... The hit-location system is also a bit unusual - because you only roll 3d6 to determine what was hit, the number of outcomes possible is not really enough in relation to the number of hit locations - which results in strange things like, on shots aimed at center of mass, people getting shot in hands and feet a lot more often than, say, in the head, and actually getting hit in the torso only about one time out of three... In a couple of cyperpunk games I've played, several grim-and-gritty combat sessions degenerated into slapstick, when after two or three dozen shots being fired by both sides, the bad guys were lying on the ground - in pain, but still very much alive - after being shot virtually ONLY in hands, feet, forearms and calves
