2x Sprint, Unlimited Sprint

Insurance Fraud level 3, Insurance Fraud level 6

Factories

Sprint doesn't seem like something you absolutely need, until you use it and find how quickly you get winded. The fact of the matter is that sprint is incredibly useful, especially when you find yourself under heavy fire and you need to run away for a minute to get some breathing room. Sprinting after cars looking to escape your attempts to jack them is also handy. Finally, play some co-op with someone that has unlimited sprint when you don't and you'll see how little fun it is to be the slow one.

Insurance Fraud absolutely needs two people even with the doubled damage requirements. When the activity starts, you'll be told to go to certain areas of a chosen district so that you can get more adrenaline when you throw yourself in front of cars, and while those areas can be helpful, the truth is that the freeways are where it's at for two reasons: tractor trailers and garbage trucks. Every time you get hit by a vehicle, you get some money and you build up your adrenaline bar. Get hit by something very large, and you get more of both. With two people doing the activity, you can have one person head to the freeway and one person head to the chosen district to trigger the start of the activity. Then, while one person starts getting hit on the freeway, the person who triggered the event can then head over to their own section of the freeway and start getting hit. Once your adrenaline bar gets maxed out, try to get hit into the air so that you can use the left stick to control the path of your body to bounce off of multiple cars and rack up big numbers. $300k worth of damage off of one pavement dive is not impossible or unlikely if you're staying on top of things. One final thing, try to keep your adrenaline bar active for as long as possible as if you have an active adrenaline bar you can still get money towards your goal, even if time has run out.

2x Health Regeneration, 3x Health Regeneration

Snatch level 3, Snatch level 6

Chinatown

If being able to regenerate is good, then being able to regenerate twice or three times as fast must be better, right? Absolutely. Grab these unlockables and you'll never need to eat another Chicken Bazoom as long as you live.

Snatch can be a pain, especially at the higher levels, however having a co-op partner mitigates that pain somewhat, or at least just let's you share it with others. In the early levels, having a co-op partner helps because you can go and get your ho's and your partner can go and get their ho's, allowing you to complete levels in short order. Once you get to the higher levels, particularly level 5 and 6, you're going to want to team up so that one person can drive and one person can shoot. The longer you take to bring ho's back, the greater your chance of having them stolen back by rival pimps, or arrested by the cops, so you need to be quick about things. Also, be mindful of who's pursuing you as you don't want to get rear-ended when dropping off a ho, as if your car gets knocked into her, she'll be killed and you won't get credit for the drop-off. If you have the money to spend on reinforcing the frame and bumpers of a four door car in your garage, it's not a bad way to go as your car will get pretty banged up in this activity.
So that's it for the Must Haves. Not so bad right? Spend a few hours and you're rewarded with the best weapons in the game, all the ammo you need to fire them, the ability to run like the wind, and recuperative powers that Wolverine himself would envy. You also have plenty of respect to do story missions should you want to, but really, why stop there? With just a few more activities you can be even better.

Nice to Haves

GAL 43 SMG, Unlimited SMG Ammo

Snatch level 3, Snatch level 6

Downtown
Rounding out the Snatch activities nets you the best SMG's in the game and more ammo than you can shake a stick it, unless you can shake an infinite number of sticks, and we're pretty sure that you can't. This is a Nice to Have as the Kobra is, essentially, a sub machine gun, and quite a powerful one at that, however the extra ammo brought to the table with twin GAL 43's certainly won't hurt. The same Snatch rules as before apply. Get a co-op partner, get a car, get some ho's, shoot anyone in your way and then do it all over again.

XS-2 Ultimax, Unlimited Shotgun Ammo

Drug Trafficking level 3, Drug Trafficking level 6

Airport

You already have the best pistol in the game, so why not get the second best shotgun? We say second best because the best shotgun, the Pimp Cane, isn't unlocked until close to the end of the game, so until then, the Ultimax will have to do.
For Drug Trafficking, you have to stay close to your dealer friend and protect him, shooting anything that moves in the process. You have unlimited pistol ammo, but you already have that from before, and if you did the Downtown Snatch activity to completion you have unlimited SMG ammo, so running out of ammo shouldn't be a problem. Stick close to your dealer, and remember to shoot the driver of incoming cars rather than waste time trying to blow up the vehicle. Drug Trafficking will have you going all over Stilwater, and as such is one of the game's more time consuming activities.

15% More Melee Damage, 30% More Melee Damage

Fight Club level 3, Fight Club level 6

Arena

You don't do a lot of melee fighting in Saints Row 2, so the ability to do more melee damage isn't totally necessary, however it is nice to have for when you get yanked out of a car and you need to teach some lessons with your fists.
Fight Club pits you against ever increasing number of combatants. Weapons are strewn about, and food is dropped from the floor to replenish your health. One very important thing to keep in mind is that your health doesn't regenerate during Fight Club so you'll have to eat to get your health back. Try to clear out any food slots taken up with non food items before starting the activity so that you're not wasting slots on things that won't heal you. When fighting, use the trash cans and cinder blocks to knock down multiple opponents at once and do not get yourself cornered or you're in for a short fight. Co-op isn't necessary in this one as any advantage to having another player is negated by having to fight more people.

5% Reduced Damage from Vehicles, 15% Reduced Damage from Vehicles

Insurance Fraud level 3, Insurance Fraud level 6

Museums
Occasionally you'll get run down by rival gangs rolling up to whatever fracas you've gotten yourself into, but for the most part, you don't get hit with a lot of cars in Stilwater. Even so, if you can get 30% fewer owies from taking a bumper to the face, why not do so? Stick to the freeways with it's copious big rigs, garbage trucks and tour buses and you and your partner will be rolling in damages in no time.

5% Reduced Damage from Bullets, 15% Reduced Damage from Bullets

Heli Assault level 3, Heli Assault level 6

Barrio

Unlike damage from cars, you do take a lot of damage from bullets as you'll be shot at quite a lot in your efforts to take back Stilwater. Still this is a Nice to Have, as the 3x Health Regeneration from Snatch trumps any reduction in bullet damage.
In Heli Assault you'll be flying an attack chopper and providing assistance to your homies on the ground by taking out rival gang members and gang cars. Co-op isn't a bad way to go here as one person flies and one shoots, however communication is key. Make use of the fact that you have unlimited mini-gun ammo and unlimited missiles and blow up anything that looks at your homies wrong. Heli Assault is one of the longer activities in the game, so make sure you have enough time set aside for all of the wanton destruction.

Flamethrower, Annihilator RPG

Mayhem level 3, Mayhem level 6

Nuke Plant

The flamethrower, while fun to use, really isn't necessary, and can prove to be your downfall should your victims run into you and set you on fire. The Annihilator, on the other hand, can be very useful as it's the only weapon with a lock-on outside of the attack chopper's missiles. Any missions that have you taking out vehicles are made supremely easy with the Annihilator.
When playing Mayhem, you need to do a certain amount of damage in a certain amount of time with longer sustained bouts of, well, mayhem, bringing damage combo. You have unlimited ammo, so don't be afraid to throw grenades and shoot off your RPG. Once the big, easy stuff has been taken down, use smaller items like fence sections, garbage and the fleeing masses to keep your combo alive. Be on the lookout for special targets that give more damage and give them priority.

5% Accuracy Increase, 15% Accuracy Increase

Septic Avenger level 3, Septic Avenger level 6

Suburbs
When you have all of the ammo in the world, accuracy really isn't something you have to worry about, however being able to save reload time by hitting what you're aiming at ain't such a bad thing Septic Avenger is so completely over the top that it's easily one of the most fun activities in the game, second only to Fuzz. You're tasked with riding in a septic truck and spraying poop over designated targets. Someone else drives for you however you can control when the truck brakes, which you can use to your advantage when you really need to coat something down. Your poop supply recharges, however it'll recharge faster if you don't spray until empty. Use the sprayer to spray your targets, however you can get extra cash by spraying other, non-targeted cars, buildings and people. You can also spray pursuing police cars and officers to get some extra cash and get them off of your back, which is essential in the later levels as your truck will explode if it takes too much damage. Co-op isn't necessary in this one but it is more fun with another person.

5% Reduced Damage from Explosions, 15% Reduced Damage from Explosions

Trail Blazing level 3, Trail Blazing level 6

Downtown

You don't get blown up a lot in the game, unless your co-op partner doesn't know which end of the RPG is the business end, so these unlockables aren't totally necessary. Still, you only need to take a Molotov cocktail to the face once to long for a smidge less damage from them
In Trail Blazing you'll be riding an ATV while on fire through a checkpoint race where time is added to your time as you set things ablaze. Because you can add time to the clock by setting things on fire, it can be worth it to take slight detours so that you can set cars and barrels alight. Also, be sure to run over the various flame piles on the ground as they'll explode when you run over them, sending gouts of flame out in all directions, adding time to your counter and patients to the local burn ward.