I posted some advice on tougher fights in the past, in the form of some advice on handling many-on-one fights, aka boss fights.
Patrick Halter posted his thoughts on the subject, and a great description of GURPS's "maneuver economy" as well.
The thing with making enemies in GURPS tough is, you have to consider different avenues at once. D&D conflates hardness-to-kill with skill in combat - Hit Dice determine your HP and how often you hit a certain AC, as well. Rolemaster conflates the hit roll and the damage roll, so big strong guys can overcome a lack of actual skill with a huge stat bonus from strength. But GURPS breaks all of this up. You need to think along multiple lines:
Make Them Skilled - You have to be skilled enough to hit, and hit regularly, to be a threat. Skill 13 is probably the bottom for anything to be considered a threat in DF - it can sometimes hit you. Skill 15 is much better, since it opens up shots to the limb with a solid chance to hit (13 or less), and you've got better than a 50-50 shot at a Telegraphic Attack to the eye or chinks in armor over the torso.
They have no skill to leverage and not much protection, either.
A 13 skill is Parry 9, and rolls against a 13 when Feinted. A 15 is Parry 10 and rolls against a 15 when Feinted. Against the same 18-skill PC opponent (low for DF, but whatever), using a Medium Shield (DB 2), the first guy loses the contest by an average of 5 points and his Parry roll is a paltry 9+2-5=6. He'll die. Second guy? He loses by 3 on average and rolls against a 10+2-3=9. Much better! Add a Retreat and he's got a 50/50 shot of not getting hit, despite being feinted on one turn and attacked on the other by a much superior foe.
Skill 16 gives the best chance at a critical hit (3-6 instead of 3-5 for a 15, and 3-4 for anything lower). Skills in increments of 2 above that give you more targeting options, and, more critically, a real chance at Deceptive Attacks that matter.
Big strong monsters only get to overwhelm defenses if they have a really big weapon, so check the rules on Parrying Heavy Weapons and their addendum in GURPS Martial Arts if you're going to want your giants to just power down defenses despite their low skill. Unless they are really big, this won't happen, and if their defenses suck, they won't get more than a chance or two.
All of this helps, because you need to hit, and often hit multiple times, to get through the defenses of a front-line fighter. Case in point, the knight in my DF game has Two-Handed Sword-24 and a Parry of 16 (he has Combat Reflexes for a +1); thanks to a two-handed sword and Weapon Master additional parries are only -1 each, so he parries three hits at 16, 15, and 14, and he'll retreat to get a further +1 if he needs it. He's not likely to miss a roll. My own knight in GURPS Midgaard has a Parry of 18 and a Block that's not much lower. Either of those guys needs to be seriously swarmed and serious hit a lot per second before they will start to worry.
What's their Dodge? Dodge isn't dependent on skill, but on speed, so it's a good back door to make a monster that's hard to whack but isn't necessarily going to hit you too often. However, since it never goes down, and gets a +3 from Retreat, don't overdo it. A flying monsters with a high dodge and good magic resistance is going to smoke a party if it's also got a lethal attack, if only because they have no way to deal with it.
Make Their Attacks Strong Enough - can the maximum damage of this monster threaten the targets it can hit? If not, it's fodder at best, and harmless at worst. If the average damage can threaten the front line fighters where it can hit them, then it's beginning to get to a worthwhile level. If it can kill with an average hit, or at least incapacitate, it's lethal. But consider the kind of DR they should be able to break through. If that monster should be able to rend plate, or those orcs are meant to chop up mail-armored warriors with ease, their damage needs to reflect it.
Arm Them Appropriately - Watch for giving armed opponents weapons with a U parry, which prevents them from attacking and defending on the same turn, unless they have some other useful defense. Make sure the weapons they have, have the reach and damage to have the effect you want. And for unarmed attackers, consider giving them a pass on getting sliced up when parried.
Ranged Attacks - Consider how this monster deals with flying opponents. Or when the PCs cast Levitate on them, move them up a yard, and then turn them around and leave them there. Consider how they deal with guys who back up all the time.
Use Tactics and Terrain - Opponents are tougher if they force you to fight on their terms. So make your opponents fight that way. Ranked fighters work well to swamp the defenses of fighters with short weapons. Front rank with reach 1 weapons and shields, second and third ranks with spears and/or polearms. Back them up with ranged weapon fire or put archers on the flanks. Build barricades. Combined obstacles, bad terrain, and hazards (oil, caltrops, triplines, green slime puddles) together to slow down attackers and keep them in a kill zone.
And for goodness' sake give them magical support. Great Haste, Blocking spells, and attack spells that don't depend on a low "to hit" roll to have some kind of effect (Create Fire works wonders this way). Darkness spells and Mystic Mist are good, too.
None of this will help fodder be more than a brief obstacle, but at least they are trying.
Special Powers - A good catch-all - monsters with Injury Tolerance (especially No Brain or No Eyes or Homogenous), monsters with high rates of Regeneration or who have immunities to attacks (Insubstantially, say, or some kind of weapon immunity) might last longer. Creatures with Extra Attacks and/or extra limbs carrying more weapons for more defenses can be tough to kill simply for the same reason PCs would be - they won't blow a roll very often.
Monsters with the right special powers can really change the threat level. This is an easy way to increase their toughness without making major changes to a creature. They can be tougher without any real additional effort - a ghost with Affects Substantial or non-physical spells vs. a party without the correct spells is going to be a TPK, even if the same spells and same creature would be fodder if they had it. Which leads to . . .
Know the Strengths of Their Enemies - pitting undead against a Holy Warrior or Cleric with True Faith (w/Turning) doesn't work out well. It's very effective and makes low-Will undead helpless against them. Pitting mass numbers of low-damage monsters against an armored knight isn't a threat, because they'll ignore their attacks - Light Plate is DR 6, DR 9-10 is easy with magic and/or Armor Mastery from DF11. Pitting low-Will creatures against a wizard specializing in Will-based spells is equally a waste of time. Know that Weapon Masters will probably hunt up enough skill to Feint at a -3 and strike at a -3 using Rapid Strike and the rules from GURPS Martial Arts and kill most moderate-skill or moderate-defense monsters in a single second. Be aware of these things when you think about how an encounter will go.
Those are some ways you can make a monster tougher in GURPS. I hope this meandering mess helps someone!