Here are some tips for giant-sized, high-strength humanoids in combat in GURPS. Mostly giants, like this fellow here, but also ogres, djinn and ifrits, big weapon-using demons, etc. It's aimed at armed striking; grappling is a big topic and it depends heavily on your skill and what rules you are using. Striking is a bit easier to deal with, but still can stump a new GM wondering how to make giants a real threat with weapons.
First, the best way to be a giant-sized fighter is to also be a highly skilled giant-sized fighter. Skill wins fights in GURPS (much like in reality), and you need some skill to fight.
No matter how high your ST, you must hit the target, and then the target must fail to defend, in order to take advantage of that damage. Miss or have the guy defend and it doesn't matter how much damage you could have done.
Second, you must be able to survive your opponent's turn. High HP from ST is nice, but against a powerful delver (such as a knight doing 3d+8 cut, like the one in my DF game) it won't keep you alive long.
But as a GM it can be painful to make giants with skill 18 or 20 just to keep up with the PCs who casually parry their attacks, feint them, and then slaughter them. It seems like too much skill, and it's implying a level of weapon mastery that might just not be appropriate. What if the giant's skill is more like 12-14? What can you do to still be a threat to human-sized delvers who have high defenses and high-powered attacks?
Throw Stuff - Familiarize yourself with the rules for throwing objects on Basic Set, p. 355. A high ST will let you throw pretty heavy stuff pretty far. The sweet spots are right between BL/2 and "up to BL" - you do the most damage at the best range. Second-best is a bit heavier. Try to get a good range and damage, and throw away. Stones, etc. are okay. Weapons are better - throwing axes, slings (swing damage!), and maces are good choices. Thrust-based attacks are second best, but can be very lethal. Throwing weapons will reduce the defense choices of your targets and limit their options to retaliate while you attack.
Heavy Weapons - Try to take advantage of the rules on Parrying Heavy Weapons (p. B376). Most human-sized (SM 0) opponents you'll face will use weapons in the 2-6 pound range (average is about 3, for a Broadsword or Small Mace). Two-handed weapons will get up into the 7-12 pound range, depending on which ones. To break these weapons, you need a weapon 3x this weight. To automatically overcome parries by these weapons, you need a weapon heavier than their Basic Lift. So get a big weapon (possible oversized - check DF1 or LTC2 for rules on these) of at least 10 pounds, preferably 15+, is a great choice. Two-handed weapon users and shield users will frustrate this, but you limit the options of the one-handed weapon parrying types significantly.
. . . but not TOO Heavy - Avoid weapons that have a U on their Parry (so you can't attack and Parry on the same turn) if possible (but see Defensive Attack below), and ones with a double-dagger indicating they need to be re-readied. Time you spend not attacking or unable to defend except by Dodge is time you are vulnerable.
Chain Weapons - Look into using a flail or chain of some kind. Morningstars, kusari, flails, or nunchaku are all good choices. Parry against them is -4, Block is -2. They are a bit harder to use but they effectively trade 1 point of skill for a -2 Deceptive Attack (-4 parry, -2 block, no penalty to Dodge). They won't help against Dodge monsters, however, but they may force opponents into dodging.
Armor Up - Armor is heavy when you are big, but you need to protect your vital areas and your legs/feet. You won't be able to last long if you can't stop a high-damage cutting attack from just sawing one of your legs out from under you. Carrying an appropriately-sized shield so you can Block missiles and melee attacks and gain the DB for your Dodge and Parry.
Okay, that's gear choices. But we still need to turn that moderate skill (12-14) into a winning skill.
Reach - use your Reach. A bigger fighter + a big weapon = a long reach. Use Wait, take steps back, etc. Sure, charging forward into the shortest possible range and doing All-Out Attacks sounds good, but it means a short life and makes giant-sized opponents nothing more than high-HP fodder. Don't be fodder. Save AOAs for right after the highly-skilled opponent Feints you badly out of position and you feel like you need to incapacitate him now to survive. Otherwise, defend first and damage second. Keeping a foe out of his easy melee range and backing up to force him to come to you can keep you out of a skilled attacker's Feint range, too, so you don't need to worry that his skill will overcome yours. Try to force your opponent to All-Out Attack, Committed Attack, or Move and Attack to reach you.
The rest of these require GURPS Martial Arts. Sorry. Basic Set doesn't give you a lot of tactical tools for strong guys. GURPS Martial Arts specifically set out to correct that.
Defensive Attack - the stronger you are, the more this costs to use. But do it anyway. Trade some of your damage for a +1 to defend, or to allow you to defend despite attacking with a Parry U weapon. Losing 1 point per die on a 5d+3 attack is trivial if it means avoiding a damaging swipe in return. Your "jab" is a knockout, so why not take the +1 to one defense for what's effectively little cost?
Fight like George Foreman did in his comeback. You know you have a one-punch knockout. So wait for the chance to throw it, and keep working on your opponent to get an opening.
Telegraphic Attack - this is your friend. You trade a +2 to your opponent's defenses for a +4 to your own hit roll. +4 turns a 12 skill into a 16 - that's the optimal - best chance to avoid a critical failure; critically successes aren't affected by Telegraphic Attack. It turns a 14 into an 18, which allows you to absorb up to 2 points in penalties for hit location, bad footing, or other assorted penalties like Shock.
But it gives your opponent a +2 to defend! This is true, but it's better to force a roll to defend than to just miss. A failed defense roll or a natural 18 (critical failure!) can only happen if you hit. So suck up the +2 and hope they fail to defend. If they do, try against - and if that defense is a Parry or a Block, all the better for Beat.
Beat - Beat is your friend. It's a ST-based feint. In order to beat, you need to have prior contact with your opponent. If they Parried or Blocked your last attack, or your Parried theirs, you can Beat. This is where Defensive Attack and Telegraphic Attack help you. DA gives you a better chance to Parry or Block, and then you can use your weapon or shield to Beat. Telegraphic Attack helps you hit, which might score past their defenses and kill the target. If they Parry or Block, you get to Beat. Beat is resisted by either DX-based or ST-based skill, so highly skilled opponents can still counter. But a ST 28 giant has an edge over anything other than a skill 28 opponent. This really helps strong opponents.
Remember that Beat affects the defenses of the target against all attackers, so this helps if you have allies (fodder, fellow giants, whatever). Set the guy up for your friends to butcher!
Beat is limited to one defense, so a two-weapon fighter (who can parry your attacks), a Dodge-based defender, or a weapon-and-shield defender can likely frustrate this approach. But it does limit the options of the defender.
Finally, Consider Rapid Strike using Extra Effort. Spend the FP to drop the attacks from -6/-6 to -3/-3 and go for a pair of Telegraphic Attacks, or a TA and Beat, or Beat and Attack, whatever. You'll need a good pool of FP to do this, however.
All of this advice applies to a lesser and lesser extent the more skilled you get. If you are a ST 30 guy with Weapon Master, Broadsword-20, and Shield-20, you're going to fight like any other skilled attacker and just have higher damage in the process. But for a moderate to low skill high strength humanoid, it's worth trying the approach(es) above to be a real threat.
I hope that helps some GMs who wonder why their players regard the ST 25 skill 12 ogre as fodder but treat the ST 13 skill 15 orcs with a little respect.