Groundwater, which is the main source of water for human consumption in many rural areas, has its quality determined by the complex interaction of environmental factors and anthropogenic activities. The present study evaluated the quality of shallow groundwater (1 to 25 m depth) in the rural area of the Târgovişte Plain, a densely populated area (200 inhabitants/km2) using 80 water samples collected from public wells. In order to explain the spatial distribution of the concentrations of the 19 physicochemical parameters considered (including heavy metals), the evaluation of groundwater quality for human consumption and potential impact on human health was conducted using the Water Quality Index (WQI), Integrated Weight Water Quality Index (IwWQI), Total Hazard Index (THI), and cumulative carcinogenic risk (CCR). For the WQI/IwWQI the comparative analysis of the two indices showed that for the WQI, it is important to select an optimal set of parameters, because use of a large number of physicochemical parameters can eclipse the values that exceed WHO guideline limits. In contrast, the use of entropy in the calculation of the IwWQI did not lead to eclipsing of exceedance, no matter the number of parameters used. Areas with poor and very poor groundwater quality according to the WQI/IwWQI overlapped, with a moderate risk to human health (THI > 1) for noncarcinogenic contaminants and also a risk of developing cancer according to the CCR average value (1.15 × 10−2). The health of 43% of the rural population in the Târgovişte Plain can be affected if they drink contaminated groundwater, and it is estimated that about 600 people can develop cancer during their lifetime. If the risk of developing cancer is reduced only in the rural population that does not have access to a water source from a centralized and verified network, the results suggest that 385 people (1.15%) can develop cancer as a result of consuming groundwater contaminated with heavy metals based on the average value of CCR. This value is lower than the general mortality rate in areas with high CCR and below the average number of cancer patients in Romania (2.65%). The quality of groundwater and the risk of developing diseases and cancer due to water consumption is directly proportional to the intensity of agricultural land use and inversely proportional to the depth of the groundwater layer, the distance from the main hydrographic network and the reservoirs, and the distance from the main city, Târgovişte. The complex and integrated analysis of groundwater quality using quality indices and indicators of health risk for the population, validated by hot-spot analysis and compared to the mortality rate, is an approach with practical applicability. This integrated approach allows public authorities, policymakers, and health services to implement an efficient monitoring program and optimize anthropogenic activities in order to prevent groundwater contamination and finally improve the quality of life for the residents in the area of this study.