In Halo: Combat Evolved, the Ghost is the best vehicle to use during the final assault on Two Betrayals before proceeding to the final Pulse Generator, however it should only be used unless you have a sound plan, recklessly running into the battle without a plan will get you killed on higher difficulties. It is a good vehicle to use when you first encounter it on Assault on the Control Room, if your able to grab it before the Elites do, it can be effective against the Wraith. Circle strafe around behind it to get shots at its weaker back section as much as you can.
In Halo 2, the Ghost is a sound option to use during the assault on Old Mombasa, the battle on the beach will provide you the fastest hit and run option when taking on Covenant forces.
Do note that when a Flood Combat Form boards your Ghost, you will not be ejected from the vehicle and will be instead hit repeatedly by the Flood Combat Form. This is similar to when the Drones board your vehicle.
In Halo 3, when you first encounter Ghosts on The Storm, it is best to take them out from afar using a Sniper Rifle or a Battle Rifle, as their power can be extremely deadly when driving in on a Warthog.
In Halo Wars, use Ghosts to collect resources or perform hit and run tactics. Beware of Base Turrets, which are the Ghost's bane.
In Halo 3: ODST, in the level Mombasa Streets, sometimes a Ghost will be dropped off by Phantoms. If you manage to hijack it, you can use its firepower and boosting ability to quickly overwhelm any Covenant forces. Then you can use it as transportation to travel the city much faster. If you have a plasma pistol, you can also EMP and board an already occupied one.
Ghosts work well in pairs, by working together two Ghosts can split an opponent's fire, allowing at least one to survive and overrun your attacker. In team games, Ghost convoys working with Wraith are extremely effective, balancing the Wraith's slow movement and rate of fire and providing excellent cover against attempted boarding by enemy players.
The Ghost is at its best on Rat's Nest. Due to the smooth terrain and the little room for foot opponents to evade, splattering is easy. Fleeing opponents with heavier weapons is also made easier with the relatively few obstructions.
As its official designation would suggest, the Ghost's speed and size also makes it an ideal recon or distraction vehicle. A skilled ghost pilot can be able to survey the outside (or inside) of a base in order to figure out a better method for attack for the rest of the team. It also serves well as a flag escort, at antagonizing the enemy team during an attempt at the flag, and as a defensive tool against possible flag theft, as a flag carrier moving on foot is a prime target either for a splatter or for plasma fire.
If you are attempting to splatter someone with a Ghost, do not boost until you are about two Scorpions' length away from them. Any farther and they will have time to either jump, or worse, stick you with a grenade or hijack you.
The best way to take a Ghost from a foe is to trick it. Dodge a Ghost and it may boost into the wall, while it backs out it can be easily boarded from behind. For additional insurance in securing the vehicle, use a Plasma Pistol overcharge or Grenade Launcher detonation (depending on the game) to short the Ghost out so it can't back away before you get close enough to hijack it.
On enclosed areas like the basement floor on Isolation, it is easy to splatter unexpected opponents, since there is little room to avoid the wide vehicle.
A strategy for rapid attack with a Ghost is available on Valhalla and Ragnarok. When driving a Ghost, enter one of the Man Cannons. Just as the nose of the Ghost touches the Cannon, activate the boost. The ensuing acceleration will propel the Ghost and player across the entire map, though the Ghost often explodes upon impact.
In Halo: Reach and only in Halo: Reach, the large cylindrical object (most likely some sort of fuel tank) on the left side of the Ghost near where a character's legs would be is explosive and is the vehicle's weak spot, equivalent to the circular section on the rear of a Wraith. As little as three shots from a Magnum can destroy the Ghost. It is very difficult to make the shots on a moving Ghost, so you could have a teammate go into Armor Lock so the driver of the Ghost has to wait to kill him, then shoot the weak spot.
Be careful about who you splatter in Halo: Reach. An Armor Lock is almost a guaranteed fatality, giving the forward guns more purpose to a careful player. Splatters are still by far the fastest way a Ghost can kill a player, however. Just not the safest.
When driving a Ghost, always try and keep the front of the vehicle pointed at the enemy. The sides and rear provide zero protection against enemy fire, and a well-placed precision weapon shot will end your joy ride quickly.