Anticlimax Boss: Amusingly, the final two bosses can both be taken down before the fight even begins, due to them both appearing on the map before the battle and still being damagable in this state. See here and here. These were fixed in the HD version, however.
Character Rerailment: After the poor reception Ratchet received from the previous game, Insomniac Games replaced his obnoxious and self serving personality from the first game with the much more heroic and altruistic one that he would have for the rest of the series.
Demonic Spiders: The Y.E.T.I. on Planet Greblin. They are everywhere, highly durable, annoyingly cheap, and will do their best to prevent you from getting moonstones, often attacking in large groups. Some developers admitted they were coded in a rush and break some of the enemy guidelines they set, like short attack telegraphing and constantly attacking from behind. This actually got a Medal of Dishonor made for the studio, called the "Snowbeast Award", for whoever made the worst thing in a game made the previous year.
Designated Hero: Angela Cross. After The Reveal, she's treated as a misunderstood hero who's been thwarted by unsuspecting dupes. Though she was a Well-Intentioned Extremist, her crimes up to this point include kidnapping and holding Clank hostage, repeatedly trying to kill Ratchet, and generally just acting like an actual villain. Though we learn she was forced to resort to extreme measures to stop Fizzwidget from releasing the Protopet in its current state when he fired her and refused to listen to her concerns, her actions cross the line from extremism to villainy quite easily.
Well, the incident of Oozla looked more like an accident (sure she did basically steal a map at gunpoint but she probably didn't realize that the thugs turned off the outpost's defenses) but everything else is pretty much a good explanation.
Even Better Sequel: Quite apart from Ratchet's improvement in professionalism and character, the weapons are more serious yet still creative, the number of worlds and gameplay elements increased, RPG-like elements such as the upgrade features were added, and the wrench controls became a lot less cumbersome. There's also a ton of new features and gadgetry, and even the Clank sections underwent some major changes.
The Bouncer can be this in all but the very last levels. It does massive damage on the initial blast and lets loose mini-bombs that seek out remaining targets and explode for additional damage. The final boss can be killed in a couple minutes just by bombarding it with Bouncer bombs.
The Plasma Coil is an okay weapon at first, hitting a primary target for decent damage and shocking nearby enemies when it hits. However, it upgrades into the Plasma Storm, which fires an orb of electricity that shoots out lightning at anything it passes. A single Plasma Storm shot is enough to clear entire rooms full of enemies. Better yet, its Challenge Mode forms upgrade its low initial ammo capacity of 15—the Mega form holds 25 shots and the Ultra form doubles that to a whopping 50! Finally, the fact that it's not affected by gravity and never needs to impact on anything to deal damage means it's great at handling those flying enemies the Bouncer tends to miss.
The Shield Charger is a magnificent example of Magikarp Power. It's initially weak and almost useless, it protects you from damage and does minor damage to enemies you touch. Stick with it though and it becomes the Tesla Barrier, which shoots lightning to zap any enemy that gets close to you, and it does good damage with it too. It noticeably helps against the above mentioned Demonic Spider Y.E.T.I.
As last time, the RYNO II pretty much annihilates anything you aim it at.
The Sheepinator makes fighting Protopets hilariously easy, killing them without using any ammo whatsoever (so you could save your ammo for the harder enemies of the level). The Black Sheepinator is even better, killing them faster and also turning them into sheep that explode.
Goddamned Bats: The Protopets. They keep reproducing if you don't get every single one of them and you often encounter them in groups.
Goddamned Boss: Megapede is not difficult to beat, but it has a large health bar, moves around the arena all the time, deploys irritating bombs en masse, and when whittled down by a powerful weapon, deploys mini-tanks with a difficult-to-avoid attack.
In first-person mode (the one you unlock after beating the game, not the "Hold L1" view), if you do a double jump and use the wrench, Ratchet will actually pop up a bit. If you are near a wall or ceiling, you can spam the wrench, allowing you to climb past obstacles and even skip Clank entirely if you so desire.
By using the above glitch, you can actually make it pretty far in the game without having to retrieve Clank. If you make it to Joba and buy the Levitator, you can still use it... it's just that you don't have Clank, which hilariously leads to Ratchet magically levitating through the air.
Using the Charge Boots on Grelbin while being attacked by the Y.E.T.I.s can cause Ratchet to disappear with only his shoes, helmet and Clank being visible. In this state he is immune to damage, which means you can run around collecting Moonstones or beating Y.E.T.I.s at your pleasure.
Ho Yay: In the first cutscene, Ratchet is told he will learn a number of bizarre skills to become a commando, including ballroom dancing. Complete with an image of him in a fancy suit, dancing with a dress-clad Clank.
The Unknown Thief's true identity, being a female lombax-like species named Angela Cross. Of course, the series' "official wiki" does not care with the spoiler policy, so only a few fans would really not know about this before playing the game for the first time.
Captain Qwark is the Big Bad, and was impersonating Fizzwidget the entire game.
Porting Disaster: The HD remaster has some... issues. Glitching, the camera being obscured and the tour of the weapons facility having the audio removed, cutting the entire tour by half.
The physical Vita version apparently crashes whenever the player enters the Space Limo to travel to a moon in Maktar Nebula. The digital version doesn't have this problem, but both might crash upon beating the Mothership, which dies with a giant explosion.
The prequel weapons available from the special vendor in the planet Barlow, which actually were very useful in that particular game, suffer a really bad case of the "Nerf Effect" / "So Last Season Syndrome" in this game and are generally next to useless when compared to your starting weapons as well as the later ones you'll eventually come across.
The Meteor Gun. While the previous gun you had (the Lava Gun) was an effective flamethrower weapon, this version merely turns into a slightly more powerful version of the Heavy Lancer with less effective range. The result is it loses its effectiveness against swarms of small foes and gets outclassed against anything else by the rest of your arsenal. In the weapon's appearance in Up Your Arsenal, it instead levels up into the Liquid Nitrogen Gun, which keeps the stream effect that the Lava Gun has.
The Scrappy: The New Age Mystic for being generally unhelpful and requiring the hard-to-get Moonstones just to do something.
The "Wrench Ninja II" skill point is just as bad, as the enemies on that planet will often kill each other before you even reach them, and it's nigh impossible to hit some enemies without getting a few scars for your trouble. Fortunately, it's possible to come back after you get the second wrench upgrade, which allows you to kill the regular mooks in one Hyper-Strike, and the big purple mounts in two, and there will also be less enemies the second time around.
That One Boss: The third battle with the Thug Leader is tough for the reason of being a Marathon Boss. Normal weapons can barely even leave a dent, and you're forced to use the turrets all over the battlefield to even have a chance of damaging his mecha. However, you'll be spending more time shooting at some homing beacons, and every time 10% of the boss's health is taken, the turret will end up destroyed, forcing you to search for another one.
Collecting the moonstones on Grelbin. The crystal-gathering sidequest on Tabora had similar problems, but at least the enemies there were manageable.
The Ace Bunyan space races, especially if you're going for the Platinum Bolt. You need to A) Collect every single ring, which have confusing hitboxes, and B) Still win the race. Fortunately, there's only 3 of these races in the game.
The Playstation Vita port accidentally makes them even harder, as the Vita has a much more sensitive analog stick, although setting camera speed to slow seems to ease it up a bit. (Unless it's just placebo.)
Underused Game Mechanic: One of the 3 new robots that can assist Clank is the Lifterbot, which can lift up blocks for Clank. Or rather, it can lift up ONE block for Clank, and then never be used again.
Woobie Species: The one-eyed robots seemingly can't catch a break. They get blown up in a commercial and eaten by mutant squirrels on Todano, killed by security robots on Aranos, and massacred on their home planet, Damosel. Two skill points involve keeping them alive despite the hordes of enemies waiting to get them.