It's easier to just use layers (then you can just fill using 'sample merged' [GIMP terminology] and a high tolerance, without any destruction -- only parts of the fill that will be visible will be the ones that aren't hidden by the lines). Alternatively, you can probably use 'behind' mode to fill achieve a similar effect. There are other modes, like Darken, that might work for you, depending on your workflow, but I disrecommend them.)
My understanding is, though, that among (semi-)professionals, it's quite common to do a totally messy brushed fill (going beyond the lines) and clean it up later by using a floodfill with only the lines layer visible, and the colors layer active (so the lines layer provides the masking information, and the BG is painted onto the colors layer). Or similarly using magic wand then Clear, if the background needs to be transparent.
Apparently there is also something called 'flatting tools' (well, the GIMP version is called that -- I know it was based on a Photoshop plugin) which does an automatic 'color-coded' fill -- a new layer with each contiguous area filled with a unique color, auto-extended under the lines until there is no 'empty space'). If you do toony stuff, this might make you happy.
Link -- also includes link to the Photoshop plugins.
