It's the bustle I like about Barcelona, so I was going to say be careful where you DO stay, because a lot of nice 4* (particularly the more business orientated ones) are in the business district or a metro journey away. I just don't want that when I want to immerse myself in a city, amongst the hubbub of it all, but it very much depends on what you want, I guess!
If you do choose to stay centrally though, I think it's generally a good idea to avoid particularly the bottom end (the coast end) of Las Ramblas which can get quite seedy after dark. I've stayed at the top, nearer Plaça de Catalunya twice, and been fine, though. And I also stayed on Passeig de Gràcia, which was very busy, a bit like staying on somewhere like Regent St, I suppose. Thankfully we had a courtyard room, though.
Gaudi is probably the biggest draw of Barcelona for me; Parc Güell in particular I would say is my absolute must. Outside of that there are a whole host of other places well worth visiting, though. It's been a few years since I last went, so I'm sure others are probably better equipped to recommend other places. And as far as nightlife is concerned, I know nothing.