I've owned an Epson 3170 for over 5 years, and recently bought a used 4990. The Epson Scan software both use has basically the same interface as the software that comes with the V500.
When I first tried scanning 6x6 negs and slides with my 3170, I tried using thumbnails, and would occasionally have problems with the software detecting the image size, and getting it all messed up. Ever since then I've left the thumbnail box unchecked. I'd just as soon crop myself.
I scan my B&W negs in 24-bit color. Why? Because sometimes I feel like playing around with things a bit in post processing, and it's possible to bring out color in subtle ways, without having to resort to the various canned tints that some image processing software has. I haven't noticed any significant difference in sharpness between scanning in color or 16-bit grayscale. Usually if I haven't added color or tint to the B&W image, I'll convert it to 16-bit in pp.
As to what options to check and uncheck, I've tried them all, scanning with and without. I prefer to have the USM checked, and this comes from processing raw DSLR files -- the more than can be done to the raw image before it's translated to a portable file format, the better. My experience has been that, while Epson Scan's USM doesn't seem to be very strong, it doesn't seem to add to grain/noise the way it does in post processing. I also check Grain Reduction usually. Again, personal preference. More often than not, I prefer fine grain over coarse. I don't use Color Restoration with B&W, even though I scan it in color. I do use CR on a case-by-case basis when scanning color slides or negs. Back Light Correction -- same thing, case-by-case basis. Often it gives a nice "pop" to an otherwise dull looking B&W image. Gotta watch out, and not blow out the highlights though. I never use Dust Removal, ever since I discovered that this "feature" actually adds crystal-looking artifacts to the scans, rendering them unusable. To be fair, I've only run into this with my 3170 and only with color slides. But they looked so awful, I've just never wanted to try it again. Maybe with a better scanner, like the 4990 or V500, or maybe with B&W this won't be as big of an issue. I don't use Digital Ice because it reduces image sharpness, and the improvements it provides are very minimal.
I scan my medium format slides and negs at 2400 dpi indicated. I find that's plenty fine enough.
Anyway, that's just what I've found works for me. YMMV and all that.
Michael