Next-to-leading order (NLO) QCD predictions for the production of heavy quarks in proton-proton collisions are presented within three different approaches to quark mass, resummation and fragmentation effects. In particular, new NLO and parton shower simulations with POWHEG are performed in the ALICE kinematic regime at three different centre-of-mass energies, including scale and parton density variations, in order to establish a reliable baseline for future detailed studies of heavy-quark suppression in heavy-ion collisions. Very good agreement of POWHEG is found with FONLL, in particular for centrally produced D 0, D + and D *+ mesons and electrons from charm and bottom quark decays, but also with the generally somewhat higher GM-VFNS predictions within the theoretical uncertainties. The latter are dominated by scale rather than quark mass variations. Parton density uncertainties for charm and bottom quark production are computed here with POWHEG for the first time and shown to be dominant in the forward regime, e.g. for muons coming from heavy-flavour decays. The fragmentation into D s mesons seems to require further tuning within the NLO Monte Carlo approach.