As a game designer there are some things about GURPS that made me twitch. I haven't played it in years, but I know the basic success mechanic is the same as always. Rather than rolling dice and adding for a total, you roll under a stat. This led to a very narrow ceiling on what was practical for attribute and skill advancement. Once a score got to 16, it really didn't matter as the odds of rolling a 17-18 on 3d6 is pretty much nill.
This is also due to the bell shaped curve and the non-linear progression that 3d6 creates. This curve created a lack of granularity and a fairly drastic decrease in risk as scores improved made for very little incentive to continuously improve.
On the contrary, the d20 system can always have someone that is bigger, badder, or better because of its linear progression and d20 + Skill mechanic.
Now I know that GURPS has ways to address this issue. But its not as simple or intuitive as the d20 system. Ironically had they inverted their success system and made it 3d6 + Stat I would probably have played it more.
The other thing that I saw was the slooooow combat and relatively low drama from the system. A good GM can compensate for this effectively, but Combat seemed very monotonous, slow, and tedious. Maybe there have been improvements to the system since I played that made combat more exciting (and I haven't played 4th ed). In fact, it seemed to reinforce the "I attack" response more so than creative description, which was also limited by the 1 second round.
Lastly, there is the appearance of complexity from the size of the book. The GURPS 4th edition book is HUGE! And frankly I don't have that much time to read through all those rules. Sure I don't need to. Only certain sections really need a good read to get started, but the illusion of complexity is there. Picking up an encyclopedia takes less effort than lifting the GURPS books LOL
These days when I consider a new game system I try to figure out how many pages that I need to read to build a character - not counting equipment or spells. If it is more than about 50 pages then I put the game down. Because GURPS has so many advantages, disadvantages, and quirks, it looks huge. That's a lot of options to filter through. Too many for a beginner. So this may be a factor for its declining popularity.
If d20 did anything right it was splitting out the player books from the GM books.