This study assessed how electronic cigarette (ECIG) characteristics amenable to regulation—namely nicotine content, flavor, and modified risk messages—impact ECIG use susceptibility, harm/addiction perceptions, and abuse liability indices among combustible tobacco cigarette (CTC) smokers and non-smokers. CTC smokers and non-smokers varying in ECIG use recruited via Amazon Mechanical Turk (MTurk) completed an online survey in 2016 (analytic n = 706). Participants were randomly assigned to one of eight conditions differing in ECIG characteristics: nicotine content (no, low, high), flavor (menthol, tobacco, fruit), or modified risk message (reduced harm, reduced carcinogen exposure). Regressions assessed ECIG susceptibility, harm/addiction perceptions, and abuse liability indices (purchase task measures of breakpoint/intensity) within each regulatory domain (nicotine content, flavor, message) and their interactions with CTC/ECIG status. Differential effects on ECIG susceptibility, harm/addiction perceptions, and abuse liability indices were observed by regulatory domain with many effects moderated by CTC/ECIG status. ECIG nicotine content and flavor conditions were the most influential across outcomes. Greater nicotine content, tobacco-flavored and reduced carcinogen exposure ECIGs were more highly preferred by CTC smokers with some differing preferences for non-users. Findings reinforce consideration of discrete ECIG preferences across tobacco use status to improve regulatory efficacy.