I do the transcodes 4 Heyuri Cytube. I use HandBrake, and the settings I generally use are:

Format
Format: MP4
Web optimized: enabled
Align A/V start: enabled
Passthru common metadata: enabled
Display size: automatic
Dimensions
Cropping: None
Resolution limit: 480p NTSC SD
Anamorphic: automatic
Optimal size: enabled
Filters
All off unless there's telecine/interlacing issues (typical on unaltered DVD rips) or too much noise (typical on BDs of cel era anime - noise is difficult to compress and bloats ur resulting file sizes, so it's best to smooth it out while trying to retain as much of the actual content detail as possible). Filters drastically slow down the whole process so I prefer to avoid them
Video
Video encoder: H.264
Framerate: Same as source, variable framerate
Color range: Same as source
Encoder options
Encoder preset: Slow (depends on how l33t ur CPU is and how long u can tolerate - the slower it is, the better job it does of compressing, but there is a point of diminishing returns)
Encoder tune: Animation (fast decode disabled)
Encoder profile: Main
Encoder level: 3.1
Quality
Constant Quality: 22 RF (depends on the show)
Audio
AAC, 160 kbps, stereo, auto
Subtitles
Burn in: enabled (browsers don't natively support softsubs, so u have to burn them in to make it hardsubbed)
Note: HandBrake does a shitty job of burning-in VOBSUB subs (image-based DVD subtitles) if the source uses non-square pixels, which DVD sources usually do. They always appear offset in the final result, especially for 4:3 shows. That's why sometimes I'll go for the OCR'd SSA subs, but that means u'll lose all the typesetting and positional info if the release group/individual didn't fix it up themselves. It's preferable to just find a release with really nice subs instead