I was having issues with sound effects being extremely faint (aside from Sam's and ambient effects), which was making play difficult since it was frequently hard to tell where enemies were coming from. None of the in-game audio settings seemed to make any difference. However, these settings in the Sam2.ini file fixed it...not sure which one exactly did it, so the possibly relevant lines are:
sfx_iAPI = 1;
dsd_bAllowEmulation = 1;
dsd_iSoftwareProcessing = 0;
dsd_iDefaultAdapter = 0;
sfx_bAllowEAX = 1;