You will enjoy this game whether you have played any others in the series or not. A very solid addition.
You will notice your good 'ol Guitar Hero gameplay, which is quite boring to talk about in any game in this series, because it doesn't change too much, ever. Same game, new box.
First off, selecting songs in a quickplay playing mode has become a lot more efficient. The first time I played a game like Guitar Hero was with a friend who owned Rock Band 2. The song selection interface was slick and easy to navigate, but when I got GH:WT, I was really unimpressed by the interface. Guitar Hero 5's upgraded interface is definitely a good point in the game.
Second, party play mode is one addition that most people will be impressed by, especially if you are the kind of guy that hosts the party. Again, I will not go too in depth about this mode, but when deciding whether or not to buy this game, keep in mind Party Play;
Third, I obviously have to talk about the song library. Guitar Hero World Tour had a library that was pretty impressive, but GH5 didn't quite live up to that, in my expectations. The library was very diverse- possibly too diverse. It went from hip hop (Feel Good Inc. - Gorillaz ft. De La Soul), to rock-pop (Bob Dylan), and then to hard rock (Smells Like Teen Spirit- Nirvana), and while this will make a quite a few of the songs appeal to smaller crowds, it will make for less of a familiar library to those who enjoyed the older GH libraries.
Final Verdict: The game, in itself, is a very solid game. There is plenty of play time here, and the gaming modes are all fun (while a couple of new modes are introduced from GH:WT). However, if you were looking for a totally new playing experience, you will not find it here; it is very similar. I still recommend this game to anyone who is a strong follower of the Guitar Hero series, an established and fun series; a reputation that Guitar Hero 5 lives up to.