Im going to run my first dark heresy 2nd edition game, Im familiar with some of the rules from my other rogue trader game but I`d like to have some advice. What can you tell me?

Explosives are a bit wimpy- you'd expect bouncing a grenade off of someone's head would kill them, but even if they aren't wearing a helmet, chances are it won't put them down. My first house-rule was adding 1d10 to all explosives (grenades and missiles).

The introductory adventure in the book has a Daemonhost in it. Some people find it extremely hard to kill, others think it is wimpy (especially for a Daemonhost). Rebalancing that might be a good idea.

Overwatch is a hot-topic; by the rules, it is extremely abuseable. Keep this in mind.

Combat deadliness is something you'll get a feel for. Sometimes it can seem brutal, but a lot of the times you may have to get creative in the tactics department to hurt your players, especially if you're attacking them with regular cultists. The introductory campaign in the rulebook is great, but does need some fleshing out (you should be able to find lots of ways to do that on this forum). It does end with a fight with a very tough boss though, so be prepared for that (protip: krak grenades).

Over watch is definitely a hot topic right now, a lot of us GMs here are experimenting with house rules (arguably rules as intended), but you probably won't run into any problems with it for a while unless your players are already familiar with the system

If you're familiar with RT, you should find DH2e a much slicker beast. It's a good system and a lot of fun, there's just a couple of quirks to be aware of. Tell us more about the game you're planning on running!

The aptitudes are not balanced, so instead of having your players design characters around what aptitudes they can get, you should be generous with letting them exchange an aptitude or two - that way you can focus more on the roleplay reasons for selecting the different home worlds, backgrounds, etc.

Im familiar with some of the rules from my other rogue trader game but I`d like to have some advice. What can you tell me?

Quick run-down on the main differences:

1. If you played Rogue Trader, you're used to Profit. Influence kind of does the same thing, but everyone has their own score - it's not communal. There is a communal score - you're inquisitor's influence (much higher) but using that may get him annoyed, especially if you keep using it without asking. It also tanks your subtlety because it represents turning up, slapping down a rosette and saying "...by the authority of the Immortal God-Emperor Of Mankind..."
2. Full auto is no longer the king of combat. Full Auto is still useful, because suppressive fire is amazing, but with non-epic characters with starting ballistic skill, semi-automatic fire is normally the best balance of getting the most hits with actually getting any hits at all. Accurate weapons remain scary as hell in the hands of a decent sniper.
3. Swift/Lighting attack have been simplified a lot.
4. Reinforcement characters - essentially you can burn influence to pull in 'a contact of yours' as a replacement/spare character for a session. This is very useful as it gives you access (at a cost) to characters who are specialists in obscure skills, or an effective combatant to assist (i.e. replace) a less violently inclined investigator.